LEPROSY:
  IN ITS
  CLINICAL AND PATHOLOGICAL ASPECTS.




  LEPROSY:
  IN ITS
  CLINICAL & PATHOLOGICAL ASPECTS.

  BY

  DR. G. ARMAUER HANSEN,
  _Inspector-General of Leprosy in Norway_,

  AND

  DR. CARL LOOFT,
  _Formerly Asst. Phys. to the Lungegaards Hospital_.

  TRANSLATED BY

  NORMAN WALKER, M.D., F.R.C.P. ED.
  _Asst. Phys. for Dermatology, Edinburgh Royal Infirmary_.

  WITH NUMEROUS PHOTOGRAPHS AND COLOURED PLATES.

  BRISTOL: JOHN WRIGHT & CO.
  LONDON: SIMPKIN, MARSHALL, HAMILTON, KENT & CO., LTD.
  HIRSCHFELD BROS., 82, HIGH HOLBORN.

  1895.




  JOHN WRIGHT AND CO.,
  PRINTERS AND PUBLISHERS, BRISTOL.




AUTHORS’ PREFACE.


As it is evident in the numerous recent publications on Leprosy that
our first work on the disease, which was published in Norwegian,
is unknown to many investigators, and as there appear in their
publications many statements, to our thinking, premature and founded
on insufficient knowledge, we think it desirable to present a
comprehensive statement of the result of our studies of this disease,
so interesting in itself and so instructive in other directions.

Since one of us has been for more than twenty years occupied in dealing
with the disease, we hope to be able to lay before experts a thorough,
complete and instructive demonstration, the more, as we do not base our
views, as has been frequently and unfortunately done, on any single or
scattered observations.




TRANSLATOR’S PREFACE.


In the translation of this little work I have, of course, made absolute
accuracy of meaning my first aim. It presents the views of one who in
his knowledge and experience of the disease is probably second to none.
There are, of course, certain points on which there is much difference
of opinion. For example, Hansen’s view, which is very widely held, of
the position of the bacilli in the cells, is very strongly opposed by
Unna. Then as to the occurrence of nodules on the palms and soles which
Hansen denies, Unna remarks that it is quite exceptional, while Hillis
seems to consider it by no means rare. The chapter on Treatment has
been wholly re-written for this edition, and is practically a summary
of the late Dr. Danielssen’s views. The photographs are a further
addition to the original German edition. It has been pointed out to me
that Dr. Hansen does not refer to the recent Indian Commission. His
views on it may be found in the _Lancet_, of October, 1893.

In conclusion, I have to thank my friends, Dr. Colcott Fox for a
general reading of the proofs, and Drs. George Mackay and Stockman for
their revision of those parts relating to the affections of the eye and
to the drugs used in treatment.

                                                        NORMAN WALKER.

EDINBURGH, _May, 1895_.




CONTENTS.


_CHAPTER I._

                                                                   PAGE

 INTRODUCTION AND NOMENCLATURE                                        1


 _CHAPTER II._

 NODULAR LEPROSY                                                      5

 Seat, 5; Localisation, 5; Affection of the Eyes, 8; Affection
 of the Extremities, 10; Affection of the Mucous Membrane,
 11; Affection of the Lymphatic Glands, 13; Subcutaneous
 Nodules, 13; Affection of Nerves in this Form, 14; Fate of
 the Nodules, 15; Commencement of the Disease, 16; Duration
 of the Eruptions, 19; Fate of the Patient, 19; Combination
 with Tuberculosis, 22; Comparison with that Disease, 23;
 Affection of the Lungs, 26; Cultivation of the Bacilli, 27,
 Miliary Leprosy, 28; Mental Symptoms, 29.


 _CHAPTER III._

 STRUCTURE OF THE LEPROMA                                            31

 Movement of the Bacilli, 31; Nature of the Cells, 32;
 Nature of the Blood Vessels, 32; Softening of the Nodule, 34;
 “Brown Elements,” 34; “Globi,” 35; Position of the Bacilli
 in the Cells, 37; Position of the Bacilli in the Blood Vessels,
 38; Effect of Measles, 40; Digestion of the Bacilli by the
 Cells, 41; Structure of the Bacilli, 41; Bacilli in the Sweat
 Glands, 43; Affection of the Testicle, 45; Affection of the
 Liver, 47; Affection of the Spleen, 47; Affection of the
 Glands, 48; Affection of the Nerves, 50.


 _CHAPTER IV._

 LEPRA MACULO-ANÆSTHETICA                                            52

 Prodromal Stage, 53; Development of Bullæ, 53; The
 Macular Eruption, 54; Symmetry, 55; Neuritis, 56; Trophic
 Disturbances, 57; Affections of the Joints, 59; Motor Weakness,
 60; Atrophy of the Interossei, 61; Paralysis of the Orbicularis
 oris et palpebrarum, 61; Trophic Affections of the
 Bones and Skin, 62; Sensation, 64; Loss of Smell and Taste,
 66; Duration, 66; Cause of Death, 66; Recovery, 67.


 _CHAPTER V._

 PATHOLOGICAL ANATOMY OF THE MACULO-ANÆSTHETIC
 FORM                                                                68

 Comparison of Recent and Old Macuoles, 68; Alterations
 in the Nerves, 70; Bacilli in the Nerves, 70; The Spinal
 Cord, 71; Lymphatic Glands, 72; Muscular Affections, 72;
 Association with Tuberculosis, 73; Necrosis of Bones, 75;
 Joint Affection, 76; Difference between the two Forms of the
 Disease, 77; Influence of Climate, 79.


 _CHAPTER VI._

 DIAGNOSIS AND PROGNOSIS                                             82

 Diagnosis from Psoriasis, 82; Diagnosis from Syphilis, 83;
 Diagnosis from Syringo-myelia, 83; Leprosy in France, 83;
 Morven’s Disease, 83; Prognosis, 84.


 _CHAPTER VII._

 ETIOLOGY                                                            86

 Humoral Pathology, 86; Heredity, 87; Miasma, 87; Contagion,
 88; Baumgarten’s Dormant Heredity, 89; Nature of
 Heredity, 90; Father Damien’s Case, 93; Leprosy among
 Norwegians in North America, 94; Inoculation, 95; Hutchinson’s
 Fish Theory, 96; Direct Proofs of Contagion, 97;
 Hospital Experience in Norway, 99; Communication of the
 Disease, 102; Greater Danger of Nodular Form, 102; Leprosy
 and Vaccination, 103.


 _CHAPTER VIII._

 TREATMENT                                                          105

 Ancient Treatment, 105; Treatment in the Eighteenth
 Century, 105; Specific Remedies--Madar 107, Cashew Oil 107,
 Gurjun Oil 109, Chaul Moogra 111, Hoang-nan 113, Ussacou
 113; Carbolic Acid, 114; Creasote, 114; Phosphorus, 115;
 Arsenic, 115; Ichthyol, 115; Kreuznach, 115; Mercury, 116;
 Iodine, 116; Tuberculin, 117; Chlorate of Potassium, 118;
 Hydroxylamin, 118; Europhen, 119; Aristol, 120; Naphthol
 and Salol, 120; Methyl Blue, 120; Nerve Stretching, 120;
 Electricity, 121; Salicylate of Soda, 122; Importance of
 Isolation, 124; Results in Norway, 125.




 TABLES.


                                                                   PAGE

 _TABLE I._                                                         128

 The Frequent Complication of Nodular Leprosy with
 Tuberculosis.

 _TABLE II._                                                        138

 The Proportion of Tuberculosis in Maculo-Anæsthetic
 Leprosy.

 _TABLE III._                                                       144

 The Proportions of the Two Forms of the Disease in
 Different Districts.

 _TABLE IV._                                                        145

 The Results of Isolation in Norway.




 LIST OF PLATES.


                                                                   PAGE

 PLATE I.--Tuberous Leprosy (the so-called Facies
               Leonina) of two years’ duration                        8

    ”  II.--Tuberous Leprosy of six years’ duration                  10

    ”  III.--Tuberous Leprosy after breaking down of
               the Nodules                                           12

    ”  IV.--Maculo-Anæsthetic Leprosy of two years’
               duration                                              55

    ”  V.--Case of Maculo-Anæsthetic Leprosy after
               Recovery                                              61

 PLATES VI. to XIII.--Chromo-Lithographs                            148




LEPROSY:

 IN ITS
 _CLINICAL AND PATHOLOGICAL ASPECTS_.




CHAPTER I.

INTRODUCTORY.


The Bacillus Lepræ has now been recognised in all leprous products,
and although the fact has not yet been experimentally demonstrated, we
may practically say with confidence that Leprosy is a chronic disease
caused by the Lepra bacillus.

Leprosy appears in two forms, which are clinically pretty sharply
distinguishable, and were named by Danielssen and Boeck “nodular”
and “anæsthetic.” This nomenclature, introduced by these authors in
their pioneer work, _Om Spedalskhed_, Christiania, 1847, _Traité de la
Spedalskhed_, Paris, 1848, is so far important as it characterizes the
common and most prominent symptoms of the two forms, viz., in the one,
the nodular eruption on the skin, in the other, the anæsthesia which
results from the widespread affection of the nerves. On the other hand,
regarded from a strictly scientific standpoint, the nomenclature is
scarcely the happiest: firstly, because the one form is named from the
eruption on the skin, and the other from the results of the affection
of another organ, the nerves; and secondly, because the nerves are
affected in the nodular as well as in the other form, though the result
of the affection, the anæsthesia, does not so dominate the appearance
of the disease.

As Danielssen and Boeck recognised, skin eruptions are present in both
forms, and since, as we shall later point out, the eruptions differ
both clinically, and also somewhat in their anatomical formation, it
would perhaps be more strictly correct to describe the two forms as
Lepra tuberosa (tuberculosa) and Lepra maculosa or lævis. But, in the
first place, it is of questionable advantage to change a universally
accepted nomenclature; and secondly, it is very frequently the case
that one sees the patient for the first time after the disappearance
of the macular eruption with anæsthesia only, so that the name Lepra
anæsthetica exactly describes the case. But in order to give to
the skin eruption in the anæsthetic form its proper place in the
nomenclature we will describe the two forms of the disease as _Lepra
tuberosa_ (tuberculosa), and _Lepra maculo-anæsthetica_. And thus we
hope to have done justice both to the founders of the scientific study
of Leprosy, and to the clinical appearances of the disease.

Danielssen and Boeck have also described a mixed form of the disease,
in which nodular Leprosy is combined with anæsthetic. Sometimes
the skin eruption disappears and the nodular form passes into the
anæsthetic, and sometimes, though much more rarely, the anæsthetic
into the nodular; and since, further, the two forms are so different
in their clinical appearances that they look almost like different
diseases, the recognition of a mixed form might appear to be justified.
But since every case of nodular Leprosy is accompanied by affection of
the nerves and anæsthesia; and the natural termination of every case
of nodular Leprosy is to pass into the anæsthetic form, if only, as
occasionally happens, the patient live long enough; and since the skin
eruptions of the maculo-anæsthetic form are characterized, just as
those of the nodular form, by the presence of the leprosy bacillus, we
regard the transformation of a case of maculo-anæsthetic into nodular
Leprosy only as a sign of the unity of the two forms, and we delete
altogether the name of mixed Leprosy. Otherwise every case of nodular
Leprosy must, at all events after some years of existence, properly be
called “mixed,” for in such cases anæsthesia is never absent.

It has been attempted to indicate as a special form of the disease
a Nervous Leprosy, in which no characteristic skin affection is
present.[1] In view of what we have noted above, that nerve Leprosy is
present in both forms of the disease, and that an eruption may be noted
at some period in all carefully observed cases of the disease, this
attempt to indicate a special nerve Leprosy is evidently wrong.

[1] See Neisser: Lepra in Ziemssen’s Handbook.

We will first of all discuss separately the two forms of the disease,
the nodular and the maculo-anæsthetic, and then proceed to demonstrate
the unity of the disease in spite of the differences in form.




CHAPTER II.

NODULAR LEPROSY.


Nodular Leprosy (_Lepra tuberosa, L. tuberculosa_) is usually easily
diagnosed by its characteristic skin affection.

The leprous nodes or nodular Lepromata are of different size and
colour; their consistence is at first firm and hard; they are but
slightly compressible, and show little elasticity. Their form is
usually semi-spherical, but they are often oblong. The smallest
nodule that we have seen was not more than 1-2 mm. in diameter, and
its appearance was so little characteristic, that we had to confirm
the diagnosis by excision and microscopical examination. The larger
the nodules, the more characteristic is their appearance. As they are
almost always seated in the cutis, the epidermis over them is stretched
and shiny; it is occasionally normal in colour, but usually at first
reddish, later becoming yellow. _The localisation of the nodules is
usually characteristic._ They are generally first evident on the face,
on the backs of the hands, and on the dorsal surfaces of the wrists,
and next on the extensor surfaces of the limbs. They are more rarely
seen on the back and nates; on the flexor surfaces of the extremities,
on the breast, abdomen, scrotum, and penis, they are quite exceptional;
and we have never seen them on the glans penis, the palms or soles, or
on the hairy scalp. Leloir has described a leprous affection of the
palms of the hands, of which he himself says that it closely resembled
a syphilide in that situation. Since Danielssen, with his enormous
experience, never saw a leprous affection of the palm of the hand, we
incline to believe that the affection which Leloir observed, not only
resembled, but actually was, a syphilide.

Here in Norway where the people often go barefoot, wading in streams,
marshes and rivers, the backs of the feet and the under part of the
calves are frequently the seat of the first leprous eruption, not so
often in the form of nodules, as of a dense, regular infiltration.
Now since, as we have noted above, the face and back of the hands are
the usual seats of predilection for the earliest appearance of the
eruption, it appears not improbable that this has its explanation in
the climatic influences on these parts, possibly influenced by the
structure of the skin, especially the cutaneous vessels. That there
are peculiarities in the structure of the tissues, which determine the
localisation of the poison, one may conclude; for certain organs are
never affected with leprosy, in spite of the fact that the poison has
evidently at some time circulated in the blood.

The face is usually especially characteristic, as the eyebrows are
almost always the seat of nodules. The nodules are sometimes isolated
though close together, sometimes there are only one or two, though
usually several, and sometimes there are no distinct nodules, but the
eyebrow is infiltrated both in length and breadth, and of a reddish
colour. Even if the infiltration is not so great that the brow appears
thickened, the reddish colour and the shadow over the eyes give to the
face a characteristic expression, and one can feel the infiltration,
if the brow is gripped between the thumb and forefinger. In these
cases the hairs persist; in more severe infiltration, and where
nodules are formed, they drop out. The forehead and cheeks usually
present a diffuse or spotty redness and burnish, and with the finger
one recognises the infiltration as an increased resistance. This
discolouration is most evident on changes of temperature, as when a
patient comes from the outside cold into a warm room. Not infrequently
the suspicion of Leprosy is aroused by this change of colour, and by
the shadows over the eyebrows, even years before more definite symptoms
appear. But in most cases one finds distinct nodules in the eyebrows
and over the countenance generally. When the nodules are numerous and
large, so that the eyebrows project far over the eyes; when the cheeks
and chin are beset with large rounded or flat nodules pressing on each
other, so as to cause deep furrows between them; when the point of
the nose, the alæ nasi, and the lips are infiltrated throughout their
whole thickness; the countenance is frightfully deformed, and there is
developed the so-called _Facies Leonina_. The lobules of the ears are
almost always infiltrated, and become red, thick and elongated. _Plate
I_ is a case of tuberous leprosy of two years’ duration, the hands
being swollen with leprous infiltration.

[Illustration: PLATE I.]

The eyes are, in the nodular form, almost always affected; nodules are
frequently present in the eyelids, the upper as well as the lower, and
are usually situated close to their margin. The earliest affection of
the eye itself, which we have observed, is a faint clouding of the
upper part of the cornea, which often appears as a very fine dotting
of the corneal surface, only noticeable when one can compare the upper
part of the cornea with the black pupil, and often requiring for its
recognition the use of a lens. A slight infiltration of the limbus
conjunctivæ is always combined with this clouding of the cornea, but it
is at this early stage so slight that it cannot be noted clinically.
Later on it increases, and gradually attacks the whole of the
outer margin of the cornea. When this infiltration becomes greater it
appears yellow, as seen through the conjunctiva running intact over
it, and this gives to the eye a peculiar woe-begone aspect. It is
quite exceptional for this infiltration to extend completely round
the cornea, for that part of the limbus directed towards the nose
is almost always free. As time goes on the infiltration increases,
and a low rampart is formed around the cornea. Sooner or later the
infiltration and nodule formation attack the cornea itself, in one of
three different ways: first, quite superficially, immediately under the
epithelium. The nodule in this case is always elevated, usually grows
very rapidly till it finally covers the whole cornea, and may by its
height prevent the closure of the lids. That part of the cornea lying
below or behind the nodule is quite clear. Secondly, the infiltration
may attack the cornea in the form of a wedge, and form a node which
is not so much elevated as in the previous instance; and thirdly, the
infiltration may penetrate the cornea close in front of Descemet’s
membrane. The result, complete blindness, is the same in all cases
when the nodule covers the pupil. A frequent accompaniment of this
form of the disease is iritis, or, as anatomical investigation shows,
irido-cyclitis. These forms of iritis run a chronic or sub-acute
course, sometimes so stealthy and painless that it is observed by
neither doctor nor patient, until adhesions have formed between the
pupillary border and the capsule of the lens. Blindness may sometimes
be caused by exudation into the pupil. _Plate II_ shows a typical case
of tuberous leprosy of six years’ duration. The hairs have completely
disappeared from the eyebrows; on the chin a few can still be seen
between the tuberosities. In the right eye is a nodule, growing from
the _Limbus conjunctivæ_ into the cornea. Nodules may also be present
in the iris, and usually arise in the outer and under margin, in the
angle between the cornea and the iris; they may completely fill the
corresponding part of the anterior chamber, are of a yellow colour,
and sometimes look exactly like an obliquely-placed hypopion, as they
have an inner or upper straight, or slightly concave margin. We once
did an iridectomy directly through a small early nodule, and put a
stop to its further growth. On anatomical examination we also find a
leprous affection of the anterior part of the retina over the ciliary
body, which appears as a fine white spotting of the retina; the ciliary
nerves are always for a considerable distance backwards infiltrated
with leprosy, as are the _membrana supra choroidea_ and the choroid
itself.

[Illustration: PLATE II.]

On the extremities the nodules always appear singly, but when
closely set may run together to form large plaques. On the backs of
the hands and fingers nodules are very frequently, and on the extensor
surfaces of the thighs and the front of the legs almost always, found.
The calves are often also infiltrated as a whole, especially on the
fibular side close above the ankle, and this infiltration reaches as
high as the middle of the leg; the skin is tense and shiny, reddish
blue in colour, and in this infiltrated part ulcers resembling varicose
ulcers readily appear, which are as difficult, if not more so, to heal.
They are surrounded by thick elevated walls, may last for years, and
occasionally completely surround the leg.

Of the mucous membranes, those of the nose, mouth, larynx and pharynx
are affected. The nasal mucous membrane is affected only in its
anterior part along with the alæ nasi and the anterior part of the
septum. If a general infiltration takes place in this situation,
the softening and ulceration which may ensue lead eventually to the
disappearance of all the soft parts of the nose; the bones are never
affected. (See _Plate III_, a case in which the leprosy developed in
1848, and was of the tuberous variety. The tubers disappeared partly
by suppuration. In 1857 he entered an asylum and then presented the
same appearances as in the photograph. He was then anæsthetic. There
were cicatrices in the face due to the disappearance of the nodules,
the point of the nose was gone, but the nasal bones were intact, thus
differing from syphilis. He died in 1885.) In the mouth, the mucous
membrane of the lips, of course, shares in the process when these are
completely infiltrated, and even on the mucous membrane of the cheeks
one occasionally sees and feels thickening and infiltration. The tongue
is often the seat of nodules, which in all respects correspond to
those of the skin. The gums, the velum, and the uvula may be either
infiltrated or dotted with nodules. The rest of the mucous membrane of
the pharynx is more frequently infiltrated than beset with nodules, and
the same is true of the epiglottis, which sometimes becomes quite stiff
and almost immoveable. In the larynx, the true and false cords are more
frequently the seat of infiltration than of nodules; the voice is rough
and hoarse, the rima glottidis is often so narrowed that respiration is
rendered difficult; excessive narrowing of the rima is only present in
the late stages, and is proportionately rare. When the mucous membrane
ulcerates the cords grow together, both anteriorly and posteriorly,
and when the infiltration disappears there remains a scar tissue,
which, by its contraction, reduces the rima to a small slit, a few
millimètres wide. In such cases a very little mucus is sufficient
almost or completely to close the opening, and the patient may perish
from suffocation. Usually an emetic suffices to open up the hole at
once; but tracheotomy is often necessary to supply air to the patient,
the attacks of suffocation are so frequent, and since he is already
voiceless, he loses nothing by the operation.

[Illustration: PLATE III.]

The lymphatic glands (cervical, axillary and inguinal) in relation
to the affected skin and mucous membrane are always swollen: this
leprous swelling is always indolent, and never goes on to suppuration.
Sometimes the glandular swelling may aid in the diagnosis, if the skin
affection is not absolutely characteristic, though this is most rarely
the case.

The nodules are almost always seated in the cutis, but they may, though
rarely, be placed deeper in the subcutaneous connective tissue; they
form then no projections, but the skin over them is almost always
somewhat hyperæmic and bluish-red, and, if the finger is passed over
the place, the thickening or the nodule may be felt in the deeper
parts. It is in our experience that a patient who had only this form of
nodules was regarded by a colleague, well acquainted with the disease,
as free from Leprosy, probably because he did not use his fingers.

From the symptoms described above, the diagnosis is almost always very
easy, and we ourselves know of no disease of the skin which can be
confounded with nodular leprosy. If necessary a piece of skin may be
removed and examined for the presence of bacilli, which, at least in
the nodular form of the disease, are never absent. This, we have once
had occasion to do.

In addition to the skin the nerves are also affected, not always at the
commencement, but always in the later stages. Whether all peripheral
nerves are affected we cannot say--certainly the facial, radial,
ulnar, median and peroneal are always diseased. According to our
investigation the nerves of the extremities are affected throughout
their whole length, but the affection is severe only at certain places,
viz., where the nerves run superficially over bones or joints, as the
median at the wrist, the ulnar at the elbow, and the peroneal where
it crosses the fibula. As a result of this nerve affection we have
pain followed by anæsthesia. The pains in the arms, hands, feet and
calves are sometimes very severe and persistent. The affection at first
causes pain, by pressure on the nerves, and later--when the pressure
has led to atrophy--anæsthesia. Now since, as we shall later clearly
demonstrate, leprous affections tend to heal, it is not infrequently
the case that nerve affections, when slight, pass off without having
specially injured the nerves, and these nerves may be the seat of
fresh infections, and thus the patient suffers from repeated painful
attacks through a course of years. This is particularly the case where
there is general infiltration of the legs, and is either the result of
repeated attacks of the same, or of the implication of different nerve
branches. The nodules are often painful when first developed, but later
on sensation is deadened.

Of internal organs, the testicle, liver, and spleen, are always
affected in this form, but we shall consider them later in the
description of the pathological anatomy.

Before we more closely describe the course of the disease, we shall
first briefly discuss the fate of the nodules. These usually remain
for years unchanged, growing very little or not at all. The skin over
and around them, or rather its vascular supply, is very sensitive to
changes of temperature, so that the skin, as we have already indicated,
changes its colour with change of temperature from dilatation of the
blood vessels. The vessels evidently suffer from the invasion of
the leprous poison. New outbreaks have often the appearance of an
“erythema nodosum,” with great hyperæmia. We had once the opportunity
of examining a piece cut out of such an erythema-like eruption, and
found dilated vessels and round cells, and only after long search a few
bacilli. One must conjecture that there is deposited with the bacilli
a chemical poison which affects the vessels, or that the bacilli
produce the poison, and that this poison has its action only in its
immediate neighbourhood.

But occasionally the nodules grow so luxuriantly that the epidermis
develops furrows and clefts which may reach down to the nodules, and
then a bloody fluid comes out of them which dries up on the surface to
a reddish brown scab. Or it may happen that the upper horny layers of
epithelium disappear, and that only a few rows of cells of the rete
Malpighii remain. In this case the exuded fluid less often dries,
the surface is usually blood-red and moist, and appears like an
ulceration, though it is not really one. When this takes place on the
face, particularly on the lips, or on the backs of the fingers, the
sufferings of the patient are very much increased. After several years
the nodules usually soften about the middle of their base, and the
nodule may sink in over the softened part; or they burst, the softened
part is thrown off, and now is developed the true ulceration by which
the nodule may be completely eliminated and sunken stellate scars alone
remain.

The determination of the commencement of the disease is exceptionally
difficult, indeed impossible, for it must always be founded on the
statements of the patient, and the patients either observe themselves
insufficiently, as may frequently be noted, or they conceal many
facts. As a matter of fact we do not know the earliest symptoms of
the disease. According to Danielssen and Boeck, the patients often
suffer long and repeatedly, before the outbreak of the disease, from
weakness, with rheumatoid pains and fever. This the patients frequently
corroborate. But we are inclined to regard these attacks of fever as
indications of the already existing disease. It appears to us more
probable that the disease begins with some form of local affection
which is so indistinct that the patient himself does not notice it, or
at least lays no weight upon it, and that these local affections are
analogous to others with which we are familiar, namely, the nodules
which may last for years before new and such definite eruptions
appear, that the disease cannot any longer be ignored or kept secret.
We believe therefore, that the patients do not really know when they
commence to be ill, and that they date the beginning of the disease
from a later eruption. If at the commencement only the extremities
are affected the patients may conceal their condition for years, and
through this concealment become so accustomed to lie, that later it is
impossible to receive from them correct information.

The cases are very frequent in which the patients have for several
years only scattered nodules, and then suddenly a fresh outbreak
of numerous nodules. The disease always advances by outbreaks of
eruptions which repeat themselves at longer or shorter intervals. It
is very often the case that the older nodules soften during a fresh
outbreak, and completely or partly disappear; and these outbreaks are
always accompanied by fever, the temperature rising to 39° or 40°
Cent. Now we know that the nodules, if the patient is affected by
another febrile disease, may disappear. It is, therefore, difficult to
decide whether the disappearance of the nodules is the cause or the
result of the eruptive fever. But we possess certain observations in
which the disappearance of the nodules has begun before the onset of
the fever, and in which, therefore, the fever and the later eruption
appear to be caused by the softening of the nodules. Supported by these
observations we regard the eruptions as auto-infections, in which
bacilli (or poison) from the older lepromata pass into the blood, and
thus new areas of the skin or other organs are affected. We have often
observed that an irido-cyclitis, or an affection of the throat, arises
during an eruption, and also that the nerves beneath the nodules become
swollen and painful, and once we have seen the testicle become swollen
and painful during an eruption. As to the affections of the liver
and spleen we have no clinical observations; they appear to cause
no clinical symptoms, or at all events, such indefinite ones that,
although our attention has been directed to them, they have escaped
observation.

_The eruptions are of the most varied duration._ Some last only a
few days and cause so little fever that the patients experience no
particular disturbance to health; they only know that a few new nodules
appear, or that they are sore about the throat. Others last for
weeks, indeed, months, with remittent fever, the temperature rising
to 40°. Quinine has no effect. During such eruptions the strength
of the patients is of course distinctly diminished, but when the
eruption is over they recover rapidly and feel themselves all right
again; only they are more leprous than before, or at least have more
leprous manifestations. The number of eruptions varies greatly in
different cases. Sometimes the patient has, for several years, several
eruptions every year; in other cases the eruptions appear only very
rarely--one or two in the whole course of the disease, and they may be
very slight. It appears as if the bacilli in different cases were of
varying virulence, or possibly the structural conditions are different
in different individuals, so that in some the bacilli (or the poison)
reach the blood more easily than in others.

Therefore the _fate of the patient is very different_. If the
eruptions are frequent the growth of the nodules is usually luxuriant,
and those nodules with diminished epithelial covering, and therefore
moist, are very frequent. If then, the whole countenance and part
of the extremities are covered with such nodules; if the eyes are
blinded by the formation of nodules in the cornea; if the tongue and
the pharynx are, through formation of nodules and infiltration, half
ulcerated and sore; if respiration is made more difficult by the
narrowing of the rima, and the voice inaudible; then the condition is
as miserable as is possible to conceive.

If there is added to this, amyloid degeneration of the kidneys, liver,
spleen and intestine, with diarrhœa, it can only be desired that death
shall put an end to such a condition, and that usually takes place
soon, although occasionally the patient may linger for months. Whether
leprosy alone is responsible for the end is, we think, doubtful; as
remarked above, the affections of the liver and spleen appear to be
without much significance.

The biliary secretion is never influenced, and there is according to
our observations no special leprous anæmia. The patients are indeed
often anæmic, or become so during the disease, but we have not been
able to convince ourselves that this is a direct result of the leprosy.
In many examinations of the blood, which were indeed undertaken for
other purposes, we have never noticed anything remarkable in relation
to the number or form of the blood corpuscles.

As in almost all cases of nodular leprosy nephritis is present, we
are inclined to regard this nephritis as a frequent cause of the
marasmus which ensues. Tuberculosis was formerly a frequent occurrence
in our hospitals, where our observations have chiefly been made. The
relationship between this and leprosy we will discuss later.

The prognosis in the case of patients in whom the eruptions appear
less frequently is more favourable, and they may live many years.
Either they die from an intercurrent disease or as a result of their
nephritis, or they become in time anæsthetic, that is, according to our
view, they recover. When the nodules become stationary they ultimately
soften, as described above, and may be absorbed without opening, though
this is rare and usually occurs only with single nodules; or they burst
and ulcerate; in either case they leave scars. If this takes place in
all the nodules and the patient is attacked by no fresh eruptions, then
anæsthesia gradually develops as the result of the affection of the
nerves; in the nerves, too, the specific leprous affection disappears,
and there remains only scar tissue, which by compression destroys
the nerve fibres and thus causes anæsthesia. Then gradually all
specific leprous affections disappear, and the patient is healed from
his leprosy, and may live many years in perfect health, having lost
practically nothing of his power of work. Such cases are unfortunately
not very frequent; but we have had the opportunity of examining some
after death and have not been able to discover in them any specific
leprous affection.

Thus one is struck with the fact, how little leprosy of itself
influences the health of the patient, and if nodular leprosy usually
shortens life, that takes place probably because in this form the
frequent ulceration leads to amyloid degeneration of the internal
organs, or that the nephritis is a sequel of the leprosy. The nephritis
appears either as the so-called parenchymatous or as the interstitial;
according to our examinations it is never bacillary. Further, as
nephritis is very much rarer in the maculo-anæsthetic form of the
disease, it must be assumed that nodular leprosy in some way causes
nephritis. The same is true of amyloid degeneration. The duration of
life of a patient with the nodular form of leprosy is in general eight
to nine years after the definite outbreak of the disease.

The most frequent complication which we have seen in our institutions
is tuberculosis, particularly some years ago, for then the
institutions were over-crowded, and consequently the sanitary
conditions were in many respects unsatisfactory.

In order to give an idea of the frequency of this complication, we
have placed in tabular form at the end of this work the results of
eighty-nine autopsies (see TABLE I, page 128).

From the statistics there given it is evident that we have had ample
opportunity of examining the combination of tuberculosis and leprosy.
Most of these examinations were indeed made in the pre-bacillary era;
but we are satisfied that the _differentiation_ of tuberculosis and
leprosy without an examination for bacilli is by no means difficult.

As Danielssen and Boeck had described a leprous affection of the
intestine, we gave great attention to this point, and as we were at
the same time engaged in an investigation on the pathological anatomy
of the lymphatic glands, we lost no opportunity of carefully examining
these organs. It was during this investigation that we discovered the
characteristic leprous affection of lymph glands, and had our attention
first directed to the leprous affection of the liver and spleen, which
affections are, macroscopically, so little evident, that we at first
overlooked them.

The leprous and tuberculous affections of the lymph glands are
macroscopically so very different, that it is impossible to confuse
them, and the microscopical differences are still more evident. Both
fresh and hardened preparations were always examined. And since the
lymph glands are always affected with leprosy, if the organs which
drain into them are affected, even if this affection is very slightly
developed, we conclude from the fact that we have never seen a leprous
bronchial or mesenteric gland, that there is no leprous affection of
the lungs or of the intestine, and later examination of certain special
preparations have only confirmed us in this view. But more of this
later, and we will first treat of the differences between tuberculosis
and leprosy.

In organs affected with tubercle one always finds, as is well known,
giant cells and caseous degeneration; in the many, we can truthfully
say, thousands of preparations of leprous affections, which we have
had under the microscope, we have never seen either a typical giant
cell with marginal nuclei or caseous degeneration. There are indeed
multinuclear cells in the lepromata, but never giant cells like those
of tubercle.

What may be the reason for this striking difference in the action of
the very similar bacilli of tubercle and leprosy, we have no idea; we
simply state the fact and assert that, if one finds giant cells, he
is dealing with tuberculosis and not with leprosy. This alone would
be sufficient to cause us to separate the two neoplasms, but there
are many other distinctions. Tubercle is avascular; the leproma is
rich in vessels; tubercle undergoes caseous degeneration, the leproma
never. Anatomically therefore, we are justified in maintaining a sharp
distinction between the two diseases.

So far as concerns the resemblance between the tubercle and lepra
bacilli, we must not omit to mention that one almost always finds
among tubercle bacilli some which are pretty long and somewhat bent;
this is never the case among lepra bacilli. Baumgarten has indicated
as a distinction between them, the fact that the latter is more easily
stained; according to our experience this distinction can scarcely
be regarded as sufficient. But the distribution of the bacilli in
the tuberculous and leprous tissue is usually so very different, the
tubercle bacilli being usually arranged singly, the lepra bacilli
always in large quantities in masses and clumps, that a confusion of
the two diseases anatomically can only be possible in exceptional
cases. Danielssen has repeatedly stated in his triennial report of
the Lungegaards Hospital that tuberculosis and leprosy are such
nearly allied diseases that the one (leprosy) may pass into the other
(tuberculosis) by a modification of the bacilli, and that thus the
frequent combination of the two diseases is to be explained. This
view we cannot, in view of the above demonstration, support. If an
organ is attacked at the same time by tuberculosis and leprosy, one can
anatomically very readily separate the two diseases. We would rather
seek the explanation of the frequent combination of the two diseases in
our institutions in the great over-crowding and consequently insanitary
conditions to which they were formerly subjected. Tuberculosis
once introduced, we find a ready explanation in the bad habits of
the patients in regard to expectoration, why it was difficult or
impossible to root it out. In later years, when the institutions are
no longer full and the sanitary conditions consequently much improved,
tuberculosis has much decreased. Whether tuberculosis was as frequent
a combination in the country as in our institutions we do not know.
The duration of life of patients in the country is about a year longer
than in our institutions, and possibly this depends on the absence of
tuberculosis.

Doutrelepont has recently described in the transactions of the German
Dermatological Society, _On the Pathology and Therapeutics of Leprosy_,
a lung affection, probably developed by tuberculine treatment, which
he diagnosed from the examination of the sputum. But the patient had a
leprous affection of the larynx, and his account by no means excludes
the possibility that the bacilli in the sputum came from a ruptured
nodule in the larynx, possibly softened by the tuberculine treatment.
We cannot, therefore, recognise this observation as infallible evidence
of the presence of a leprous lung affection, any more than that case
of leprosy of the lungs described by Bonome in _Virchow’s Archiv_,
Bd. C. That author himself draws attention to the great resemblance
of the affection to tuberculosis, and as it is quite evident from
his description of the bronchial lymphatic glands that they were not
leprous, and he notes the presence of giant cells in the pathological
products, we cannot doubt that it was really a case of tuberculosis.

In the same case there was found an affection of the spinal cord, from
which Bordoni-Uffreduzzi cultivated on glycerine agar an organism which
he recognised as the lepra bacillus. Here we may remark in the first
place that we have never seen a leprous affection of the spinal cord,
and have never found bacilli in it. We must indeed admit that we have
only examined the spinal cord in a few cases, because there appeared
to be no indication for such an examination, since clinical symptoms
do not point to an affection of that organ, and as in the profusely
nodular cases, affections easily recognised appear everywhere, except
in the liver and spleen, it was to be expected that an affection of the
spinal cord would have been recognisable. In necrotic bones, which
we have often examined, nothing leprous is found. This necrosis is
therefore no specific leprous affection, but a secondary one. Secondly,
we must remark that in spite of many attempts we have never succeeded
in cultivating lepra bacilli on glycerine agar. We therefore believe
that Bordoni-Uffreduzzi has cultivated tubercle bacilli instead of
lepra bacilli. The only thing which speaks for the leprous nature of
the lung affection and the cultivated bacilli, is the circumstance that
the author did not succeed in inoculating guinea pigs and rabbits with
tuberculosis. But, according to all investigations on tuberculosis,
it appears to us not incredible that the tubercle bacilli may, under
circumstances, become so weakened that they are no longer pathogenic.

Arning has described a miliary leprosy, and found in the products of
this disease giant cells, and also leprous ulcers in the intestines.
Dr. Arning has kindly sent us some preparations of this miliary
leprosy, in which we find evidence everywhere that the case is one of
tuberculosis, both because giant cells are found everywhere, and the
bacilli are only present singly, and scattered. They are never present
in the excessive numbers, and have not the arrangement, which they
usually have in leprous products. In connection with the presence of
giant cells in leprous products, we may note that we have received
from two foreign colleagues preparations in which they believed giant
cells to be present. But we have found, on careful examination of
the preparations, that they were cross and oblique sections of blood
vessels, which with their endothelial nuclei gave the impression of
giant cells. Without the use of a homogeneous immersion lens it was not
possible to make a definite distinction.

According to our observation there exists a sharp anatomical
distinction between leprosy and tuberculosis, and there is no such
thing as leprosy of the lungs and intestines, the bones and the
kidneys. In order to establish a differential diagnosis in doubtful
cases, we recommend in the case of the lungs and the intestines a
thorough examination of the bronchial and mesenteric glands. We
ourselves have never sought in vain, in cases of these affections, for
tuberculous or caseous degeneration in the glands, and we have seen in
no single case anything resembling leprous affection of the glands.

So far as concerns the central nervous system, Danielssen noted that
he had several times seen acute hydrocephalus in leprosy. We once saw
severe cerebral symptoms with maniacal attacks. The patient, who was
taken into a lunatic asylum, left this later, cured. Other indications
of an affection of the central nervous system in leprosy are unknown
to us. Anatomically, we have not been able to recognise in the nervous
system any traces of leprosy. In connection with this, we may note that
we have several times seen pain and swelling of the knee joints during
eruptions, which at their conclusion disappear. In these cases there is
nothing to be made out anatomically. When we reflect that, as indicated
in describing the eruptions, the bacilli and (or) their toxines most
probably circulate for some time in the blood, it is remarkable that
the organs above referred to are not affected by leprosy. We can give
no reason for this; connective tissue, which is especially liable to be
affected, is present everywhere.




CHAPTER III.

STRUCTURE OF THE LEPROMA.


The leprous nodes have on section a smooth, white, glistening surface,
if they are still sufficiently young. If one examines, microscopically,
sections or teased preparations of fresh nodules, one sees little else
but cells, with distinct nuclei, usually of the size of a white blood
corpuscle, or rather larger. There are also a few larger so-called
epithelioid cells, with larger nuclei, and among the cells, fragments
of connective tissue and of blood vessels. With a higher power, one
sees in the fluid of the preparation small straight rods, which are not
destroyed by addition of potash. These are the lepra bacilli, and thus
were they first discovered in the year 1871.

If one teases out preparations in osmic acid solution, or soaks a
nodule in the solution some hours before teasing, the rods are coloured
faint brown, and one finds them lying mostly in the cells (_Plate VI,
Fig. 1_). If one adds water to a fresh preparation, the bacilli move
actively; even in the cells swollen up with water, one sees the bacilli
moving; and this led us to regard them as movable, although we at the
same time indicated a doubt whether the movement was not simply a
molecular one; for the movements were equally vigorous in strong osmic
acid solution as in water, and on the addition of glycerine or strong
solution of albumen to the preparations, the movements ceased. All
later observers, with the exception of Unna, regard the bacilli as
motionless. We have no ambition to decide this question, because we
know no absolutely trustworthy distinction between molecular movement
and independent movement of the bacilli.

The older the nodules become, the more large multinuclear cells are
found, and in nodules of the skin and cornea one always finds small
flat cells with processes, and with oblong nuclei, which we recognise
as the connective tissue and corneal cells (_Plate VI, Figs. 2_ and
_3_).

The protoplasm of these cells is clear, while that of the round cells
is more or less granular. The nuclei of the latter are also round, and
usually very granular; the flat cells are much less stained by carmine
than the round cells, and one sees the flat cells lying on connective
tissue bundles. The nodules are richly supplied with blood vessels; in
the nodules of the skin it cannot be determined whether the vessels
are newly formed, or only those already present in the cutis. They
are, however, always of embryonic type. One sees very plainly their
formation from cells, and in the cornea, indeed, the vessels _must_
be newly formed. Here the vessels penetrate into the cornea before the
nodule forms, and round these vessels, penetrating into the cornea,
there are always visible collections of cells which are apparently
migrated white blood corpuscles (_Plate VI, Fig. 4_).

One meets also in old nodules, among apparently only unproductive
elements, blood vessels surrounded by young cells (_Plate VI, Fig. 5_).
This appears definitely to favour the view that the tumour cells are,
at least for the most part, migrated blood corpuscles. These results
have been obtained by examination of fresh nodules, and of those
hardened in Müller’s fluid. As we have recently, while hardening the
nodules in Fleming’s chromic and osmic acid mixture, and staining the
sections with hæmatoxylin, been unable as yet to find any mitoses, and
further, have found, by bacillary staining of an old section from a
corneal node, an appearance like _Plate VI, Fig. 7_, we must maintain
provisionally that in the lepromata the new formations are, at least
chiefly, formed by the immigration of white blood corpuscles. As the
round cells infiltrate the connective tissue, the fibres are pressed
asunder, and form a network closely resembling that of a lymph gland
with nuclei in the angles (_Plate VI, Fig. 6_).

When the nodule softens, which takes place almost always exactly in the
middle, it attains a brownish tint, which is due to the transparent
softened part. If one divides the softened nodule, the central part
has a distinct brown colour, and the constituents of this part readily
fall out. If this is examined under a microscope, one sees, almost
exclusively, larger or smaller clumps of a brownish colour, and very
granular. They are partly elastic, but partly brittle and fragile, so
that by pressure on the cover glass they are easily broken up. One
often sees clearly that the clumps lie _in_ the cells, the nucleus and
the cell substance being still evident (_Plate VII, Fig. 1_). Sometimes
only one lies in a cell, which then has the appearance of a signet
ring, in whose circle the clump lies, but sometimes several lie in
one cell. One finds similar clumps in all other organs affected with
leprosy, as in the liver, the spleen (_Plate VII, Fig. 2_), the nerves,
lymphatic glands, the testicle and the eyes (_Plate VII, Fig. 3_,
which shows two clumps from the retina). In the nodes of the skin, but
particularly in the testicles, one may find them so large that they may
even be seen by the naked eye. Both in the small and the larger clumps
there are usually vacuoles, not infrequently several. From the cornea
we have often got preparations in which the corneal corpuscles are more
or less completely filled with brown granules (_Plate VIII, Fig. 1_).
One sees here definitely the cell nucleus in the middle of the brown
granular material.

We have described these elements as we first observed them in fresh
and carmine-stained preparations, in which they stand out very
definitely, as the brown masses do not take up the carmine stain.
These brown elements, if one knows their characteristic appearance,
may very well serve as diagnostic indications for leprous affections,
for, according to our experience, one never fails to find them except
in very young nodules. Since the discovery and easy recognition of
the lepra bacillus, they have indeed lost their value as diagnostic
signs, unless one is examining perfectly fresh preparations. Later
investigation has proved that these brown clumps are nothing else
but collections of lepra bacilli broken down into granules, and they
have received from Neisser the well-chosen name of “globi,” as they
usually appear in spherical form. Unna declares, in accordance with
his view of the position of the lepra bacilli outside the tumour cells
in the lymph spaces, that these “globi” are collections of bacilli in
the lymph vessels, and that the vacuoles have arisen from the falling
out of bacilli in the middle. In particular, Neisser, Touton, and we,
ourselves, have opposed this view, in that we have all seen the bacilli
definitely in the cells, and have figured them so. In view of the
above description of the discovery of bacilli in fresh preparations and
of these brown clumps, there can scarcely be any doubt of the position
of the bacilli, and of the cellular nature of the brown clumps.
Further, it may be noted that in the testicles the “globi” are chiefly
in the lumen of the seminal canals, where no lymph vessels exist, and
if Unna says of the “globi”[2] that “no one has certainly determined
their cellular character,” he must have said this in ignorance of
our earlier publications in Norwegian. The above description and the
drawings were published by us in 1869 and 1870, in the _Nordiskt
Medicinsk Arkiv_.

[2] Unna, zur Histologie der Leprösenhaut; in Leprastudien, Monatshefte
für practische Dermatologie, Ergänzhungsheft, 1885.

In connection with the vacuole, we have found in a testicle a
“globus” with vacuoles, and in the vacuoles small granules which were
recognised as remains of the nuclei (_Plate X, Fig. 2_). We add to
this the picture of a “globus,” or rather a developing “globus,” with
two nuclei, from a skin nodule (_Plate VIII, Fig. 4_). We have seen
earlier, however, that the brown clump may lie in the cell without
enclosing the nucleus, and also that the nucleus may lie in the middle
of the brown mass. Now, if the vacuoles are transformed nuclei, as we
believe, then it would be comprehensible that the vacuoles would be
absent in many “globi,” and that in others which have developed from
multinuclear cells, several vacuoles would be found. That appears,
at least, the simplest explanation of their presence. But there are
certain very small “globi” with vacuoles, such as are represented in
_Plate VII, Fig. 2, c_, and those small vacuoles can scarcely represent
nuclei; small “globi” may however arise, as is evident at _x_ and _x^1_
of the same figure, from clumps of bacilli in the cells. The vacuoles
of the larger “globi” of _x_ and _x^1_ may indeed possibly represent
nuclei, but not the vacuoles in _Plate VII, Fig. 2, a-k_, nor the
vacuole in one of the small “globi” in _x^1_. Possibly the vacuoles
are also the result of a specific degeneration, either of the bacilli
themselves, or of the cell protoplasm lying in the middle of the group
of bacilli, but on this we would rather not express an opinion.

We have repeatedly demonstrated the position of the bacilli _in_ the
cells, and explained them in diagrams, but in many preparations it
is impossible to distinguish where the bacilli lie. The best method
of definitely noting their position, which we know, appears to be
the fixing of small nodes or small pieces of organs in Fleming’s or
Müller’s fluid, with subsequent dehydration and hardening in alcohol;
sometimes one gets excellent preparations by simply hardening in
absolute alcohol. If the preparations are stained with fuchsin,
and counter-stained with methyl blue, or still better, stained with
gentian violet, decolourised by Gram’s method, and counter-stained
with Bismarck brown or with Bismarck brown and eosin, one will never
fail to see the bacilli lying definitely in the cells (_Plate VI, Fig.
8_). Even in such preparations there are many places where one cannot
definitely distinguish the position of the bacilli; but as one always
finds bacilli in the cells where the preparations are sufficiently
clear, we may safely conclude that the bacilli lie everywhere _in_ the
cells. In the connective tissue spaces one often sees bacilli in and
round the nuclei of the connective tissue cells (_Plate X, Fig. 8_),
and although the body of the cell is not visible, we may conclude that
the bacilli lie in the cell body, and not free in the lymph spaces. We
have found in many sections of the blood vessels in a testicle (_Plate
X, Figs. 5_ and _6_), and in a liver (_Plate VIII, Fig. 6_, and _Plate
IX, Fig. 1_), white blood corpuscles filled with bacilli, and in both
cases only slight affection of the organ, and we also observed many
bacilli in the endothelium of the vessels, as Touton and Unna have
observed in skin nodules where we, we may remark in passing, have never
seen them. From these observations we draw the conclusion that these
two organs have been infected through the blood. As we do not know the
manner and method of the primary infection of the organ, we must devote
our attention to the search for discoveries like those described above,
and to the localisation of the bacilli in general, in order to form an
idea of the method of action of the bacilli.

As we have already noted, we found in the examination of an excised
piece of a recent eruption, in a nodular case of leprosy, chiefly,
round cells surrounding dilated vessels, and only after long search, a
few bacilli. It thus appears not improbable that during the eruption
a toxin (which is circulating in the blood), and only a few bacilli,
escape from the vessels at various places, or, it may be, only the
bacilli, which produce the toxin locally; that further, the toxin
causes the emigration of white blood corpuscles, and that the escaped
bacilli only after some time slowly increase in number and gradually
fill the cells. From the presence of the bacilli in the endothelium
of the vessels and in the connective tissue cells, one may speculate
that the bacilli are passively forced into them by the blood or lymph
pressure; we have certainly found, in the testicle referred to,
bacilli free between the red blood corpuscles in the vessels (_Plate
X, Fig. 7_). Such a fresh eruption may remain stationary or slowly
develop into a nodule, or it may apparently completely disappear,
and only after several years again become apparent, it may be
during a fresh eruption. We fancy that in these cases a few bacilli
are deposited at the time of the first eruption, and that they have
needed years to become so much increased that a permanent nodule
has finally formed. That the vessels receive lasting injuries from
the leprous infection, appears to us to be proved by the following
observations. In an epidemic of measles in one of our institutions,
we saw in anæsthetic patients the previous leprous spots, which had
long disappeared from view, definitely reappear, the _hyperæmia_ and
turgescence being on these places general, so that the earlier spots
stood out as well defined, red, and somewhat swollen areas. All this
appears to point to the fact that the bacilli increase very, very
slowly, and that possibly they also produce a toxin, usually only in
small quantities, which causes no particular injury to the organism,
since the patients, in spite of numerous nodules, with millions or
milliards of bacilli, may remain in pretty good health for years. We
may also conjecture that the toxin which is produced, usually only
acts immediately around the bacilli, leading to dilatation of the
vessels and favouring the migration of white blood corpuscles. Only
occasionally does the production of toxin or the multiplication of the
bacilli appear to become so vigorous that toxin and bacilli get into
the blood and cause an eruption; possibly this is favoured by peculiar
anatomical conditions, for it is very striking with what varied
frequency eruptions appear in different patients. That the bacilli
in the nodules are all of them dead, as has been assumed, we cannot
admit, so long as the nodules still grow. It appears to us preferable
to ascribe the character of the disease to the relative benignancy and
slight viability of the bacilli, as Unna has already suggested. As we
believe, as explained above, that the bacilli lie almost exclusively in
the cells, the question arises whether the cells digest the bacilli,
or not. As we often find cells with only one or two bacilli, and as we
find in most cells balls or clumps of bacilli, we must admit that the
bacilli multiply in the cells. In some cells the bacilli remain lying
in separate collections, in others they fill the entire cell body, but
they never penetrate into the nucleus. Finally, the bacilli break down
into small granules, and this breaking down corresponds, according to
our view, to a degeneration of the bacilli. Unna and Lütz have indeed
stated that this granular appearance of the bacilli is constant, and is
a mark of their structure, that they really consist of small rows of
cocci, and Unna has therefore described them as coccothrix. This actual
(!) structure of the bacilli, however, only becomes evident under the
action of free iodine. But we have seen in our preparations, however
they were treated, _smooth and granular bacilli lying close to each
other_, and we cannot, therefore, corroborate the view of Unna and Lütz.

Neisser first drew attention to clear spaces in the bacilli; these
Neisser regards as spores; we regard them as the first sign of breaking
down of the bacilli into granules, and for the following reasons. We
have made numerous attempts to cultivate the bacilli, and have attained
in all our investigations only (the breaking down of the bacilli into)
granules, and in examining a piece of a nodule which lay eight days
on broth peptone agar, found all the bacilli beset with clear spaces.
And as the result has always been the breaking down into granules, we
believe we are right in regarding the appearance of these holes as the
commencement of degeneration, and that we are not as yet familiar with
spores of the lepra bacillus. It appears as if all bacilli in time
break down into granules, particularly in the internal organs, where
it occurs much earlier than in the skin nodules; whether this is the
result of digestion on the part of the cell, we cannot say; but as the
bacilli at first multiply in the cells, and the breaking down appears
most definitely and freely when the cells are crammed full of bacilli,
it is equally possible that it is the result of diminished nutrition,
and as they break down more rapidly in the internal organs, it is
also possible, indeed probable, that the higher temperature in these
organs favours this disintegration. As we have unfortunately not been
able to cultivate the bacilli, it is at present impossible to form a
conclusion. At all events, we regard the transformation into granules
as a degeneration, and believe that the bacilli thus altered are dead.

In the skin nodules we have only once found bacilli in the epidermis;
this was in a nodule with many fissures in the epithelium, and partly
covered with exudation. We have not been able to decide from our
preparations whether the bacilli lie in the epithelial cells or only
_between_ them, possibly enclosed in wandering cells.[3] Touton found
bacilli in the epithelium of the sweat glands, and he and Unna in the
hair sheaths also; this situation of the bacilli we have never observed
with certainty, and it can only be exceptional, and can scarcely give
origin to a “constantly flowing bacterial spring,” as Unna suggests. As
a rule, no bacilli are found in the epithelium.

[3] In a nodule, with exudation, which we have recently examined, we
have found bacilli in the epithelium, and there are in several places
distinct leucocytic nuclei in the bacillary groups, thus showing
emigrated cells with bacilli in the epithelium.

Of the presence of bacilli in affections of the eye, it may be said
in general that everywhere, where infiltration is present, bacilli
are found. In the clouding of the upper part of the cornea described
above, which we recognise as keratitis punctata, there are found groups
of granularly degenerated bacilli close under the epithelium. This we
have only once been able to determine on the living by excision of
a lamella of the cornea; in this case the affection was, according
to our own view, disappearing, because the bacilli were granularly
degenerated. This corresponds with the fact that this characteristic
affection of the cornea always ultimately disappears; the granules are
probably absorbed. We have already stated that blood vessels precede
the nodule into the cornea, and that they are surrounded by round
cells. Here, as in the middle of the nodule, the corneal corpuscles
are found apparently intact or filled with brown granules (_Plate VI,
Fig. 3_, and _Plate VIII, Fig. 1_). The same is the case in nodules in
the iris, in which one finds the stellate cells intact (_Plate VIII,
Fig. 2_). Round cells are also found in the spaces in the cornea near
the nuclei of the corneal corpuscles (_Plate VIII, Fig. 3_). All this
appears to us definitely to indicate that at least most of the cells of
the growth are migrated white blood corpuscles.

Dr. Boeckmann has introduced, in the treatment of the nodules growing
into the cornea, the division of the cornea in front of the nodules;
through the scar formed by the healing of the wound, they hardly ever
grow. We have seen such a case in which, on the one side of the
scar, no actual nodules, but only a clouding appeared, and we were
later able to examine the eye anatomically. The nodule reached like a
rampart close up to the scar, and all its cells were full of bacilli.
On that side of the scar in the clouded part of the cornea, there
were found only a few scattered cells containing bacilli; no vessels
had penetrated the scar, and only a very few cells had succeeded in
making their way through. The treatment is therefore a very desirable
one in order to preserve the pupil free. We have been able to prepare
no bacillary preparations from the _retina_, as we have not seen the
affection since the discovery of the bacilli; the two brown clumps
which are figured in _Plate VII, Fig. 3_, lay in the outer granular
layer of the retina.

As already indicated, the testicles are affected with leprosy in all
nodular cases. The affection is both inter-tubular and intra-tubular.
In a testicle only slightly affected, we found bacilli everywhere in
the endothelium of the vessels, and in several dilated vessels white
blood corpuscles filled with bacilli (_Plate X, Figs. 5_ and _6_);
and in some places also bacilli lying free between the red blood
corpuscles (_Plate X, Fig. 7_). At the same time, and especially where
the affection is more marked, the bacilli penetrate into the seminal
canals, and lie grouped in their walls around the nuclei (_Plate IX,
Figs. 4_ and _5_, _Plate X, Fig. 1_), and their epithelial cells are
more or less filled with them (_Figs. 1, 2_ and _4_).

The bacilli appear rapidly to break down into granules, and one finds,
especially in the seminal canals, globi, sometimes enormously large,
as if they were formed by the running together of several epithelial
cells. We have found here globi where a nucleus and a little protoplasm
were evident (_Plate X, Fig. 3_), and a globus where there lay in the
vacuole small fragments stained with Bismarck brown (_Plate X, Fig.
2_). As it has been proved that a man affected with nodular leprosy may
beget children, and as the globi lie in the seminal canals, it is not
altogether impossible that these may be thrown off with the spermatic
fluid, and that in this way the ovum is infected. But as, according to
our view, these globi contain only broken down and degenerated bacilli,
it must be regarded as very doubtful whether they are still infective.
In examining the contents of the seminal vesicles, we have found in
them neither bacilli, nor globi, nor any spermatozoa. It is an old
conception that lepers suffer from satyriasis. This is, according to
our experience, certainly not the case. The leprous testicle is finally
completely destroyed by the scar-like contraction of the connective
tissue, and one finds only here and there traces of the seminal canals
around the globi which they enclose.

When the liver is severely affected with leprosy, there are evident
macroscopically, fine white, or yellow, streaks or points, which shine
through the capsule and are more evident on the cut surface (_Plate IX,
Fig. 2_); they evidently lie in the acini. One also finds round cells
with bacilli along the portal vessels and in the capsule of Glisson.
Here and there we find also scattered bacilli in the acini, and as is
evident from a specimen hardened in Fleming’s solution, the bacilli lie
in the endothelium of the blood vessels (_Plate IX, Fig. 1_). In the
liver cells we have never seen bacilli, but we have found here also, in
the vessels, white blood corpuscles containing bacilli (_Plate VIII,
Fig. 6_, and _Plate IX, Fig. 1_).

The affection of the spleen may also be recognised macroscopically
by the yellow streaks and points in its substance (_Plate IX, Fig.
3_), but the affection must be pretty severe to be recognised
macroscopically; the cut surface is then somewhat dry. The affection
has its seat in the arterial sheaths and the Malpighian bodies; and in
this organ also one can in good preparations definitely recognise the
position of the bacilli in the cells (_Plate VIII, Fig. 5_).

The glands in the hilum of the liver are, when that organ is affected
with leprosy, definitely leprous, and the affection of the glands is
often more evident than that of the liver itself. In the hilum of the
spleen we have once or twice found leprous lymph glands.

This leprous affection of the glands is macroscopically very readily
recognisable. The glands are swollen as a whole, without any alteration
in their form. On section, one sees the ampullæ and the medullary
cords of a yellow or yellowish brown colour; this colour gives to
the glands such a characteristic aspect that they can hardly be
mistaken. The affection is best studied on the inguinal glands, and
the retro-peritoneal ones in connection with them. The lowest inguinal
gland is always most swollen, reaching sometimes to the size of a
pigeon’s egg; the ampullæ and trabeculæ are coloured throughout a deep
yellow; but the somewhat thickened capsule and the connective tissue
framework have retained their greyish semi-transparent appearance, so
that the structure of the gland stands out very clearly, especially if
the lymph sinuses are injected with blood pigment, which is sometimes
the case when there have been peripheral hæmorrhages in the nodules.
As we advance upwards the glands are gradually less swollen, and the
yellow colouring of the ampullæ and trabeculæ less intense, and one can
further follow in the retro-peritoneal glands a gradual diminution of
the affection until, about the level of the kidney or rather higher,
normal glands are once more met with. The glands are permeable, but
penetration is evidently more difficult, for the lymph vessels leading
to them are dilated, especially those of the lowest and most swollen
glands.

With great patience and moderate pressure one can succeed in
artificially injecting the lymphatics without causing extravasation.
It may even be the case that only one, or at most one or two ampullæ
are affected. Microscopically the ampullæ and trabeculæ are found more
or less filled with brown bodies or globi. These are evidently lymph
cells which have become filled with bacilli and their degenerative
products--granules.

One could hardly have a better demonstration of the functions of
the lymphatic glands, as filters, than in these leprous glands. The
circulation through them is not arrested; nevertheless, the glands
retain the infectious product, and if it pass one gland it is arrested
and retained in the next. Sometimes the quantity of this infection is
so small that one or two ampullæ are sufficient to retain the whole
of it. This indicates that the circulation in the gland does not
take place exclusively through the lymph sinuses, but that the lymph
reaching the gland must at once enter the ampullæ. A similar process is
seen in tubercular lymphatic glands, in which one often finds only one
or one or two ampullæ infiltrated with tubercle.

In the nerves the bacilli are found partly in round cells, which lie
around the vessels and between the nerve fibres, and partly in the
cells of Schwann’s sheath; here also they break down into granules, and
in time completely disappear. The finer details of the affection of the
nerves are best studied on the ciliary nerves when the eye is affected,
because there one can examine the finest nerves without cutting
sections or putting them through any manipulation which might injure
them. One often sees the myelin sheath pressed in by bacilli or cells
filled with granules (_Plate XII, Fig. 2_), and one finds nerve fibres
without a myelin sheath and with a more or less atrophic axial cylinder
(_Plate XII, Fig. 1_). These drawings clearly explain how the pressure
on the axial cylinder at first causes pain, and later, when atrophy has
set in, anæsthesia. And one can also understand that when the leprous
affection passes off without complications, the axial cylinders are
again restored and become functionally active.

But on those places above referred to, where the nerves run
superficially over bones or joints, and are exposed to pressure and
stretching, secondary inflammation is added to the process.

While the primary leprous affection hardly appreciably thickens the
nerves, the secondary inflammation causes a very marked thickening.
The ulnar nerve at the elbow may attain a diameter of 7 to 8 mm. or
more, and when the secondary inflammation disappears the connective
tissue contracts, and the previously thickened nerve becomes thinner
than normal. This whole process usually advances very deliberately,
and years are required before anæsthesia is developed to its full
extent. While the section of the thickened nerve is quite smooth and
of a pale brown colour from the numerous globi present, the section of
the atrophic nerve, though also smooth, is as pale as the section of
a tendon. It consists almost exclusively of connective tissue; every
trace of bacilli has disappeared, and one sees hardly a suggestion of
nerve fibres. The leprous affection is healed, but only a completely
functionless rudiment of the nerve remains.[4]

[4] Just as the manuscript of this treatise was completed, a year
and a half ago, we obtained at an autopsy a lung in which there
was tuberculosis, but at the same time probably leprosy also. Most
unfortunately the bronchial glands were not preserved for microscopical
examination. Dr. Lie also permits me to state that he has found leprosy
bacilli in two kidneys and in one lung. He had diagnosed tuberculosis
of the lung, but at the autopsy he found only an indurating pneumonia,
containing lepra bacilli, and no tuberculosis. In the kidneys, of
the same case, he found lepra bacilli in the glomeruli, and in the
interstices between the cortical tubules. He will describe the case
more fully later. This is a mere preliminary note.




CHAPTER IV.

LEPRA MACULO-ANÆSTHETICA.


This form of leprosy was first distinctly and well described by
Danielssen, who called it _L. anæsthetica_; but since the macules, as
Danielssen recognised, play an important and constant _rôle_ in the
course of the disease, we prefer the name maculo-anæsthetica, as it
includes the two most striking symptoms; the name _L. nervorum_ used
by many investigators, we do not consider satisfactory. Certainly the
nerves suffer most, and the neuritis is the most prominent feature in
the disease, but the skin affection is a bacillary one, which precedes
or accompanies the neuritis; it is _not_, as is often believed, a
tropho-neurosis, as we have determined by the demonstration of bacilli
in both young and very old leprous patches.

Thus there disappears the sharp distinction between the two forms of
the disease--the tuberous and the maculo-anæsthetic. We must regard
them as the same disease, only with varied intensity in the action of
the bacilli.

One can distinguish in the maculo-anæsthetic form, different stages in
the course of the disease, but in general they cannot be very sharply
defined from one another.

In the prodromal stage, which is of very varied duration, lasting
for months or even years, the patients state that they suffer from
exhaustion, general debility, rheumatoid pains of the joints or
muscles, hyperæsthesia of the skin, neuralgic pain of certain nerve
regions, sopor and mental depression. Ephemeral eruptions of spots
are admitted; and pigmentary anomalies, sometimes atrophic, sometimes
hypertrophic, were noted by Bidenkap.

Danielssen states that he has seen, at the very beginning of the
disease, a slight vaso-motor disturbance, which is indicated by a
bluish-red reticular appearance, which is evident most clearly on
changes of temperature. These vaso-motor disturbances, which appear
as slight patches which can be induced by friction, are chiefly
characteristic of the maculo-anæsthetic, though they may appear during
the earliest stage of the tuberous, form.

In fact, our view is that the so-called prodromal symptoms are nothing
more than the earliest, indefinite, undiagnosable phenomena of
infection.

One or more eruptions of pemphigoid bullæ may occur in the commencing
stage, but we have more often seen them later, both accompanying the
patches and in the stage of anæsthesia and mutilation.

After a longer or shorter period the typical picture of the
maculo-anæsthetic form develops; the spots either appear stealthily or
they may appear all at once with marked fever. Several forms of the
eruption are described by investigators; in our patients usually only
the erythematous and the yellowish or brownish pigmented ones have been
noted. Usually both forms are seen on the same patient, for the simple
erythematous spots become in time more and more pigmented--usually
only at the periphery, where a bluish-red play of colours is often
seen. Those eruptions which are all along pigmented and which develop
very gradually, we have particularly noted in the intercostal spaces.
Various forms--round, oval, gyrate--have been observed. The patches may
be perfectly flat, or slightly elevated. The size varies from that of
a pea up to that of the palm of the hand, and they may be even larger.
At the commencement, we have usually found these patches hyperæsthetic;
anæsthesia is only found in the older patches. They do not always at
once attain their full size; we can often observe their growth; one may
run into another, and then the initial form is lost. The number and
extent of these patches are very varied; some patients present great
map-like eruptions on the face, back and extremities; in others the
patches are few and scattered. The seat of these patches corresponds
in general to that of the nodules, but the back and the intercostal
spaces are frequently the seat of patches, while on these areas nodules
are only rarely, if ever, present. _Plate IV_ gives a good picture of
the patches in the maculo-anæsthetic form--duration, two years. The
white centres and the slightly elevated reddish edges are very well
shown. A symmetrical distribution of the patches strikes one, and has
been regarded as indicative of a central localisation of the leprous
poisons of which the patches are a tropho-neurotic vaso-motor symptom;
but in many cases there is absolutely no symmetry, and the discovery of
bacilli in the patches themselves proves them to be the direct result
of the action of the lepra poison. The lymphatic glands corresponding
to the position of the patches are always swollen, and the swelling
may persist long after the disappearance of the patches. The duration
is very varied; some are gone in a few days or even less, others may
last for years. Pigmentation of the periphery and pallor of the centre
indicate that the patch is already old, and the pallid centre is always
anæsthetic, the anæsthesia affecting all, or only some perceptions.
The signs which Hillis indicated, as diagnostic of the patches of the
anæsthetic from those of the tuberous form, we cannot recognise. The
patches of the tuberous form are certainly usually thicker, indicating
a greater degree of infiltration, than the anæsthetic; but as both are
caused by the lepra bacillus it is evident that they may be absolutely
similar.

[Illustration: PLATE IV.]

_The longer the disease lasts the more does the neuritis predominate_;
the ulnar and peroneal trunks may be felt to be thickened, they are
sensitive to pressure, and, if carefully felt for, the peripheral
finer branches may be felt as delicate thickened cords. In one case
we were able to feel the cutaneous nerve branches in a patch, growing
daily more and more thickened, in contrast to the large not especially
affected nerve trunk. The large palpable nerve trunks are not equally
thickened in their whole length, but the thickening appears about the
joints where the nerves run across bone.

The symptoms of this neuritis are various; at first neuralgia, and
later, widespread anæsthesia, with trophic disturbances, such as the
formation of pemphigoid bullæ; we have often seen hydrarthrus and
pains in the joints. Motor pareses and paralyses are never absent, but
they are not, as Neisser argues, due to a leprous affection of the
muscles, but are a secondary neuritic symptom, as we have discovered
from anatomical examination of the muscles. As the neuritis especially
affects the peripheral nerve trunks, we find the secondary symptoms
in the peripheral regions, usually only in the extremities and on the
face. We will now more closely consider the various nervous symptoms.

Neuralgia is usually present in the extremities, in the ulnar and
peroneal regions. The anæsthesia relates to the different qualities
of sensation, and is not only present in the patches, but progresses
gradually from the periphery toward the centre, so that at last the
whole extremity, and often also parts of the trunk, become anæsthetic;
the face is always more or less anæsthetic. We have often found thermal
anæsthesia present alone, or accompanied by anæsthesia or analgesia.
The anæsthesia may become more and more extensive, or it may very
gradually disappear, indicating that the neuritis of the affected nerve
has disappeared.

Trophic and vaso-motor disturbances are never absent if the neuritis
is pronounced and lasts for any time; the skin may become œdematous,
or it becomes thin, shiny, and slightly scaly (glossy skin). We
have often seen, especially if the neuritis has lasted long, and
the later symptoms such as mutilation have commenced, dark-coloured
hyperkeratoses, usually symmetrical on the front of the leg, or on the
dorsal surface of the hands. In one patient we observed on the toes
horny, thick (1.5 cm.) symmetrically placed formations, which when
thrown off left a new-formed rosy-red skin, with intact sensibility;
the patient had on the front of the leg the appearances of ichthyosis.

The changes in the nails are a part of the trophic disturbance; they
become thickened, brittle and cleft, and sometimes thin and diminished
in size, as one finds them, as we shall see later, in the terminal
stages. The secretion of sweat is affected, being diminished over the
anæsthetic areas, and the hairs there are altered and fall out.

We regard the pemphigoid bullæ as a trophic symptom; they may appear at
the very commencement of the disease, along with the macular eruption;
but they usually appear late when the anæsthesia has become extensive;
in this we agree with Danielssen. Neisser and Leloir give prominence to
the early appearance of pemphigoid bullæ, Neisser believing that the
irritation of the commencing interstitial neuritis causes this trophic
symptom. Our reason for regarding them as trophic symptoms is that we
have never been able to find bacilli in the bullæ we have examined,
not even in those which appeared at the same time as the maculæ, and
their marked symmetry is also in favour of their nervous origin. The
bullous eruptions usually appear suddenly. The patients will discover
on awaking, one or more blisters which may be already burst; some have
pain and fever for hours or days before their appearance; (Leloir).
They vary in size--they may be small, from the size of a pea to that of
a bean, or as large as the palm of the hand.

Their contents are serous, but if the bullæ persist, they become
purulent. They usually rupture early and heal, leaving behind them
violet-coloured scars, which after some time become pale. If irritant
factors are added, if the bullæ last long and become purulent, there
develops after rupture deep ulceration, most frequent on the hands and
feet.

Bullous eruptions of the mucous membranes, which Leloir has noted, we
have never been fortunate enough to see.

We regard also as tropho-neurotic vaso-motor symptoms the acute
rheumatoid affections of the joints, which are not infrequent in our
hospital. The joints, especially the small ones of the fingers and
hands, and also those of the knee and ankle, become painful and tender,
and on palpation, a collection of fluid can usually be recognised. The
affection is always symmetrical.

These affections of the joints, which belong to the earlier stages of
the disease, usually appear simultaneously with the macular eruption,
and disappear with it, but they may appear later; and after one, or it
may be only after several attacks, thickening of the ends of the bones
and ligaments, with stiffening of the limbs, is developed. Leprous
affections of the tendon sheaths, which Wolff refers to, we have never
seen. The contracture of the fingers and toes is not tendogenous, so
far as we can decide from clinical and anatomical investigation; it is
myogenous, the leprous paralyses, which we shall immediately describe,
being the cause.

Hillis claims to have recognised a motor weakness in the prodromal
stage of the disease, and considers that the nerves are already
affected with the leprous virus. Such a weakness referable to a
neuritis of the motor nerves we have not noted previous to the
macular eruption and the onset of the anæsthesia. If there are, in
the prodromal stage, muscular weaknesses, we are inclined to regard
these as symptoms of the general weakness; according to our view, the
skin affection is the _first_ definite symptom of the disease. The
muscular affection may always be definitely recognised as a secondary
symptom by the atrophy, and the altered electrical reactions. Different
degrees and varied extent of the muscular affection may be noted;
trivial paresis with only very slight atrophy, which, along with the
anæsthesia, may completely disappear, if the neuritis passes off
without destroying the nerve fibres; and almost complete paralysis with
great atrophy of the muscles.

Paralysis with atrophy is most marked on the hands and forearms,
feet and calves, and on the face.

[Illustration: PLATE V.]

The interosseous muscles, of the hands and feet atrophy, so that the
interosseous spaces appear as furrows. The thenar and hypothenar
muscles also disappear, and the first interosseous space becomes a
depression. The muscles of the forearms and calves also atrophy and
lose their power, but complete paralysis is never developed; the
patients can always move their hands and walk. In the face, all the
muscles atrophy and lose their power, and thus all expression is
lost. The masseter muscles occasionally, though very rarely, become
so atrophic, that the lower jaw drops, and must be retained in
position by a bandage. Paralysis of the _Orbicularis Oris_ leads to
dropping of the under lip, and to extreme difficulty in closing the
mouth, and consequent escape of saliva. (See _Plate V_--a case of
maculo-anæsthetic form completely cured and anæsthetic. The maculæ were
developed in 1857, and the patient is still alive.) Paralysis of the
_Orbicularis Palpebrarum_ renders the closure of the eyes impossible,
and paralytic ectropion of the lower lid is developed. The results
of this on the eye we will refer to later. The muscular atrophy is
by no means always symmetrical; one hand may present marked atrophy,
while the other is tolerably useful. This indicates the peripheral
development of the paralysis, as does the fact that the muscular sense
is preserved, and in particular that no ataxic symptoms appear. The
patients can do fine knitting and needle-work with their paretic hands.
Their gait has a peculiar character, from the difficulty with which the
weakened muscles raise the feet, but they can both stand and walk quite
well with closed or bandaged eyes. As we shall see later, this clinical
observation corresponds with the results of the anatomical examination
of the cord.

Along with the paralysis and atrophy of the muscles, there appear
also, as the result of the destruction of the nerve trunks, _trophic
affections of the bones and of the skin_. The changes in the skin have
been already described; when the anæsthesia is advanced, there always
appear ulcerations under the heel and the ball of the foot. Most of
these owe their origin simply to pressure; the weight of the body is
too much for the atrophic skin. They are always callous, heal with
great difficulty, and so long as the patient goes about, not at all.
The ulcers are not usually deep, but it may happen that they penetrate
as far as the bone, and lead to necrosis. But usually necrosis of
the bones is preceded by periostitis, and when the pus makes its way
out, an ulceration leading down to necrotic bone is formed. We have
sometimes seen the formation of a blister precede the ulceration, but
it is rare, and it is certainly not true, as stated by many authors,
that ulceration of the sole is always preceded by a bulla. Not only
on the feet but also on the hands, necrosis with exfoliation of bone
takes place; the phalanges are especially attacked. When the atrophy
of the muscles is advanced, the fingers are always claw-like, with
extension of the first phalanx. The joints consequently often _appear_
swollen, although no joint affection is present. The phalanges and the
metacarpals undergo simple atrophy, becoming very thin at the middle,
and since the joints retain almost their normal thickness, they appear
swollen by contrast. As already noted, this clawing of the fingers is
accompanied by no disease of the tendon sheaths. The bones in the feet
undergo the same form of atrophy.

If, in addition to this atrophy of the bones, which was first noted
and demonstrated by Prof. Hjalmar Heiberg, there ensues necrosis
with exfoliation of whole phalanges or metacarpals (the carpal bones
very rarely necrose), there is great mutilation of the hands and
feet; all the fingers of the hand may go, and there remain on the
diminished carpus only small, soft processes, each supplied with
a nail--the remnants of the fingers. The toes disappear from the
feet, the metatarsal bones atrophy, and several of the tarsal bones
may exfoliate; so that ultimately there remains of the foot only a
pyramidal cushion at the lower end of the leg. In most cases we must
regard external injury as the cause of these necroses. The patients
feel nothing when they injure themselves; they may burn their hands at
a stove without noticing it. Under such circumstances it is not to be
wondered at, that inflammation is readily excited, especially as the
vitality of the parts evidently diminished. But it is remarkable how
well operation wounds heal. One may do pretty extensive necrotomies,
and the wounds heal well and quickly, either by granulation or by first
intention. In such operations it is a frequent experience that the bone
is reached before the patient feels anything, but he immediately feels
pain when the periosteum is scraped or the bone attacked with forceps
or saw. We believe, however, that it is only nervous individuals
who complain of _pain_; though it is certain that when the bone is
meddled with, something is _felt_. Probably in this connection may be
explained the statement of the patients, that when walking they _feel_
the ground. It is easy to demonstrate that a patient who is quite
unconscious of any irritation on his skin, can perceive deep pressure
fairly well.

These necroses and trophic disturbances, together with the muscular
contraction, cause the _mutilation_ characteristic of the last stage of
the disease, which was at one time described as a special form, _Lepra
mutilans_.

We said above that the finger joints _appear_ enlarged on account
of the atrophy of the shaft of the bone. In some cases, however,
the joints, especially the ankle, show changes which must either be
regarded as the remains of the rheumatoid affections of the eruptive
period, or as trophic articular changes, corresponding to those seen in
_Tabes dorsalis_. We have seen ankles and knees, but especially ankles,
presenting such an appearance. In some cases post mortem examination
shows widespread tuberculosis of the synovial membrane and of the ends
of the bones, which we shall refer to more particularly under the
pathological anatomy.

As we have already mentioned, the eyelids can no longer be closed
on account of the paralysis of the orbicularis palpebrarum, and
consequently the under part of the cornea remains uncovered during
sleep. This leads to a punctiform drying of the epithelium of the
cornea, and further, to an injection of the conjunctivæ at the under
margin of the cornea; then the vessels gradually attack the cornea,
which becomes opaque, at first around the xerotic spots, and later in
its whole under part. It may go on to ulceration with rupture of the
cornea and prolapse of the iris, and finally to complete atrophy of the
globe. As a result of the paralysis, the lower lid is always ectropic,
at first at its inner end, and later, completely. As the lower punctum
is thus drawn away from the bulb, the tears run down over the cheeks,
and the paralysed countenance looks still more woe-begone.

In the later stages, when the facial paralysis is very pronounced, the
senses of smell and taste may be very much diminished, or completely
lost.

We often see symptoms which are not proper to the disease itself
developing during its course, such as obstinate cardialgia, acid
pyrosis, and vomiting of a slimy nature indicating gastric catarrh.
Diarrhœa or chronic obstruction is by no means rare, nor is albuminuria
dependant on parenchymatous, interstitial or amyloid nephritis.

The course of maculo-anæsthetic leprosy is essentially chronic. Cases
usually last between ten and twenty years; some may even exceed forty.

The patients often die cachectic, without one being able to find on
the post mortem table any definite cause of death, or they may--though
in our aseptic and antiseptic times more and more rarely--perish from
septicæmia or pyæmia. Pulmonary or general tuberculosis was formerly a
frequent cause of death, which, however, usually takes place from some
intercurrent disease.

In the ordinary course of the disease the macular eruptions disappear,
and the neuritic symptoms--anæsthesia, muscular paralysis and atrophy,
and necrosis of bone--appear. Sometimes, though rarely, there are
several macular eruptions after the disappearance of the earlier
maculæ, or there may be an eruption of nodules. If, then, these
eruptions are auto-infections, they are evidence in favour of the unity
of the disease, in spite of the difference in form.

Where the bacilli come from, in these, so to speak, later eruptions,
when there is no skin affection, it is difficult to say with certainty.
In a case of maculo-anæsthetic leprosy we found the inguinal glands
leprous, although no skin eruption was present. Possibly, then, fresh
eruptions develop from the glands when the original skin eruption has
disappeared. Thus the specific leprous affections gradually disappear,
and only their results remain--in other words, _the leprosy is healed_.
Most maculo-anæsthetic patients become in time purely anæsthetic; they
no longer suffer from leprosy, _but only from its results_. The late
eruptions show, however, how difficult it is to define the fact of
recovery, for when all externally diagnosable signs of actual leprosy
are gone, bacilli may still remain somewhere in the body, in the
lymphatics, or possibly in the liver and spleen.




CHAPTER V.

PATHOLOGICAL ANATOMY OF THE MACULO-ANÆSTHETIC FORM.


The maculæ exhibit generally the same anatomical characters as do the
nodular lepromata, viz., infiltrations with round cells, epithelioid
and spindle cells. The difference between them is quantitative; in the
macular infiltration the number of bacilli are less. We will describe
the microscopical appearance of macules of different duration.

In a _recent_ (three weeks old) macule, microscopical examination
showed cord-like and rounded infiltrations of the cutis, with round
and epithelioid cells, mostly arranged around the vessels. There were
_pretty numerous_ bacilli lying between and also definitely in, the
cells; here and there were found little collections of bacilli or
bacillary granules, with one or more nuclei--small globi--in their
neighbourhood, which in size could not be compared with those found
in the tuberous form. Specimens hardened in perosmic acid showed
unaffected nerve fibres, which the leprous infiltrations did not
implicate. Gold preparations showed a marked increase in the number of
Langerhans’ cells in the epidermis, which, indeed, we expected, since
we agree with Ranvier in considering them as wandering cells, and not
as nervous elements. Definite changes in the cutaneous nerves were not
evident.

Microscopical sections from an older spot (perhaps two years old)
show here and there infiltrations in the cutis--especially around the
vessels, consisting of epithelioid, round and spindle cells. Bacilli
were found here and there--one or two in each infiltration. In the
lumen of one small vessel we found a collection of round cells, with
a bacillus among them; and on the inner side of the wall of another
vessel we saw a similar appearance. Gold preparations of this macule,
which was definitely anæsthetic, showed slight changes in the small
nerve twigs in the cutis, less marked precipitation of the gold salt in
the nerve fibres, and a number of Langerhans’ cells.

Sections from a very old anæsthetic macule showed only very slight
infiltration along the vessels; the cells were mostly spindle-shaped;
only a few were round or epithelioid. In most of the sections no
bacilli were found; in some, one or two distinct bacilli and some
granules, taking the same stain.

The maculæ are therefore like the nodules, leprous infiltrations of
the cutis, consisting of round epithelioid and spindle cells, the
latter being more numerous the greater the age of the macule. These
infiltrations appear to proceed from the vessels. Lepra bacilli are
always present, but are most numerous in the younger macules. In young,
not as yet anæsthetic, macules, the nerve twigs appear unchanged;
in the older ones they are usually affected. Langerhans’ cells are,
according to our view, wandering cells, and their number is probably
dependant on the inflammation.

We have only had the opportunity of examining the nerves in this form
of the disease in old cases, and have not found bacilli in them,
but merely great increase of the interstitial connective tissue and
disappearance of the nerve fibres. Dr. Arning has, however, as is well
known, found bacilli in a piece of ulnar nerve which he removed during
life from an anæsthetic patient. Our results, therefore, correspond
with the proposition put forward above, that the leprous affection
disappears, and that the anæsthesia is a result of the atrophy of the
nerves caused by secondary shrinking. We found on a mutilated finger
the collateral nerve almost completely transformed into fibrous tissue,
not a single medullary fibre being evident. In a case where on account
of joint disease (which proved to be tubercular) we amputated, the
small periosteal nerve twigs were much degenerated; in another, where
the foot was amputated for gangrene, the small peri-articular nerves
also showed degeneration.

Danielssen found, in some cases, changes in the spinal cord which,
using the methods of investigation then at his disposal, he regarded as
degenerations and inflammations of leprous origin.

Armauer Hansen, Neisser and Leloir have not been able to find any
leprous affection of the cord. The cases with changes in the cord,
described by Langerhans and Steudener, were, in our view, _not_
leprosy. Tschiriew’s case, _Lepra tubero-anæsthetica_, presented no
marked changes.

Looft has found, in two cases of maculo-anæsthetic leprosy,
degeneration of the posterior columns, atrophy of the posterior roots
and fibrous degeneration of the spinal ganglia, with disappearance
of the medullary fibres, and changes in the nerve cells. In these
two cases the affection appeared to be primary in the ganglia, and
secondary in the cord. Lepra bacilli were not found in either case, but
Chariotti found them once in the cord, and Suderkowitsch in the spinal
ganglia.

From all this we can only conclude that the cord is affected in some
cases, in others not; _definite clinical symptoms_ are absent, and
where they suggest a central cause, they may be equally well ascribed
to a peripheral neuritis.

The lymphatic glands related to the affected skin are swollen, but not
nearly so much so as in nodular leprosy. After death one usually finds
the glands but little swollen, and their appearance presents nothing
characteristic. In only one case of maculo-anæsthetic leprosy have we
found the inguinal glands distinctly leprous, and that two years after
the disappearance of the macules. This indicates in the first place
that the affection of the glands is due to the same cause in this as
in the nodular form, and secondly, that the leprous affection of the
glands may last longer than that of the skin. In the same case we
found indefinite traces of leprous affection of the liver and spleen,
unfortunately so indefinite that we cannot say with certainty whether
the liver and spleen are affected with leprosy in this form of the
disease. The case occurred in the pre-bacillary era.

The _muscular affections_, paralysis and atrophy, play a prominent
_rôle_ in the maculo-anæsthetic form of the disease, and the anatomical
examination of the muscles is of great interest since some (Neisser)[5]
regard it as a specific leprous process, while G. and E. Hoggan[6]
had previously described it as secondary, and due to the neuritis. In
our[7] examination of various stages of muscular atrophy, we have
found that the changes begin with a multiplication of the nuclei of the
_Perimysium intern._, which becomes thicker and thicker; at the same
time the muscle fibres become thinner, they retain their transverse
striation, and some break up into discs. The greater the thickening of
the perimysium the thinner become the muscle fibres, so that one must
regard the process as an atrophy due to pressure. The intra-muscular
nerves showed interstitial neuritis.

[5] Virchow’s Archiv, Bd. C. III.

[6] Archive de Physiologie, Bern. 1882.

[7] Zeitschrift, par D. C. Danielssen, Bergen, 1891.

Where the atrophy was very pronounced, as in the small muscles of the
hands and feet, the muscular fibres had completely disappeared, and
only fat and connective tissue remained. We found no bacilli, not even
in sections of very early stages of the process, where the larger
nerve branches, relating to the part, contained numerous ones, either
in so-called mixed or in true tuberous cases. We must therefore with
Hoggan regard the muscular affection in leprosy as a secondary one,
caused by neuritis. We have tabulated at the end of this work the
results of thirty-six post-mortems on maculo-anæsthetic lepers (see
TABLE II, page 138).

In those thirty-six cases we find _simple meningitis_ twice,
_tubercular meningitis_ once, _solitary tubercle in the cerebellum_
once, and _hydrocephalus internus_ twice. The protocol notes nothing
further.

The spinal cord twice showed macroscopic changes (thin and atrophic
once, thickening and hyperæmia of the lumbar cord once).

The most of these brains and cords, which are entered as normal, were
unfortunately only examined macroscopically.

Two cords thoroughly examined by Weigert’s method showed degeneration
of the posterior columns.

The peripheral nerves were probably examined in all cases, but only the
results of a few of the examinations are noted.

The lungs were found tubercular thirteen times, the intestine four
times, once without the presence of pulmonary tuberculosis being noted,
this making fourteen cases of tuberculosis out of thirty-six--almost
exactly 39 per cent. In the nodular form we had thirty-six undoubted
tubercular cases out of eighty-nine--rather over 40 per cent. Possibly,
and indeed probably, some insufficiently described cases in this form
were also tubercular, but the frequency of tuberculosis is so nearly
equal in both forms, that there is no ground for supposing that the
particular form of leprosy has any relation to the development of
tuberculosis. Under precisely similar conditions, in our institution,
the nodular and maculo-anæsthetic cases were pretty equally attacked by
tubercle. If Leloir means to say that tuberculosis is much rarer in
the maculo-anæsthetic form, than in the nodular, it is certainly not
the case in our leper hospitals.

So far as concerns the _necrosis of the bones_, the panaritii and
periostitides, we have found in them nothing specific; we have often
sought for bacilli, but always in vain. Pyogenic cocci, usually the
staphylococcus aureus, we have found both microscopically and in
cultivations.

The mutilation of the bones may occur from concentric atrophy alone,
as demonstrated by Prof. Hjalmar Heiberg (_Klinisk arbog_, III). The
phalanges of the hands and feet, the bones of the metacarpus and
metatarsus, and even the carpal and tarsal bones, diminish in all their
dimensions, evidently from trophic changes, the result of the neuritis.

We have been able to examine anatomically a few of the cases of
articular affection referred to above, but we have not seen instances
of the acute affections on the post mortem table. R. Thoma has
described clinically and anatomically a case of _lepra tuberosa_
(_Virchow’s Archiv_, Bd. 57), in which first the elbow, and later the
knee joint, was affected. Examination of the knee joint showed an
inflammatory irritation of the nature of hæmorrhagic gonitis. Where we
have noted joint affections in the maculo-anæsthetic form we have only
noted a condition of hydrops. The chronic affections we may indicate
as tubercular and tropho-anatomical. Tuberculosis attacks the joints
of lepers by no means infrequently, as is easily explainable in the
case of those already tubercular, by the frequent traumata to which the
anæsthetic and paretic lepers are exposed. The carpal and tarsal joints
are most frequently affected; but we have also seen the knee and elbow
tubercular. The process is exactly the same, as in those who are not
lepers. Chronic trophic joint affections are by no means so rare as was
formerly believed. Prof. H. Heiberg has (_loc. cit._) drawn attention
to this, and has described a foot which resembles that described by
Charcot as _pied tabétique_. According to Heiberg a characteristic of
these leprous tropho-neurotic joint affections is swelling and laxness
of the capsule of the joint, a wearing away and atrophy of the ends of
the bones, or _periostitis ossificans_, and hypertrophy of the ends
of the bones, which is especially seen in the tarsal and metatarsal
joints. We have been able to confirm these results of Heiberg’s, and
have also seen in such an ankle, growth of the synovial membrane
with villous projections; the capsule of the ankle joint was loose
and lax, the talus smooth and oblique, the cartilage worn away; and
marked outward subluxation of the foot was present. Other older spirit
preparations showed changes in the joint capsule, which was flabby and
loose or thickened, and further, slight irregular thickening of the
synovial membrane, and thickening of the ends of the bones.

We have also in some cases examined the tendon sheaths; but never, even
when contraction had existed for a long time did we find any anatomical
changes, which pointed to a tendo-vaginitis. Leloir and Wolff have
noted this clinically, but we have been unable to confirm their
observation.

The pemphigoid bullæ we have repeatedly examined, and never found
lepra bacilli in their contents; both microscopically and on culture
we have found only pyogenic cocci, usually the staphylococcus aureus.
Müller found (according to Neisser, _Virchow’s Archiv_, Bd. 103) lepra
bacilli in the contents of a pemphigoid bulla. This was probably a mere
accident. For other morbid changes found in maculo-anæsthetic leprosy
the reader is referred to TABLE I, page 128.

_Maculo-anæsthetic leprosy is therefore characterized by an infection
of the skin and nerves directly caused by the lepra bacillus, and by
secondary tropho-neurotic affections of the muscles, bones, and joints,
the skin and organa sensus._

As is clear from the description of the two forms, the leprosy bacillus
is found in the leprous products in both, though in much greater
quantity in the nodular than in the maculo-anæsthetic form. The course
of the two differs; in that in the nodular form eruptions constantly
recur, and thus the affected areas are much more numerous than in the
maculo-anæsthetic. Whether the liver, spleen, and testicle are attacked
in the latter form we cannot as yet say with certainty. In one case of
maculo-anæsthetic leprosy, we noted an affection of the throat exactly
corresponding to that constantly present in the nodular form, and in
another we found the inguinal glands affected with leprosy in a manner
similar to that in the nodular form. In the maculo-anæsthetic form
eruptions are also present, but they are by no means so frequent or so
severe as in the other. Both forms may recover. As we have frequently
noted in the description of nodular leprosy, the bacilli in the leprous
products break up into granules which finally disappear, and there
remains of the leprous products only a scar in which nothing leprous
can be recognised. Occasionally this takes place in all the affected
parts, and there remains only a widespread anæsthesia, the result
of the nerve affections; and in the maculo-anæsthetic form this is
the regular termination of the disease. In both cases the leprosy is
completely healed.

We are thus enabled to see how complete is the parallel between the two
forms. The course of the disease, especially the eruption, gives to
it evidently the character of an _infectious disease_. In the nodular
form, where the bacilli are present in millions or milliards, the
eruptions or auto-infections are frequent; in the maculo-anæsthetic
form, where their number is comparatively insignificant the eruptions
are rare.

_Does this difference between the two forms depend on a difference in
the virulence of the bacilli?_ This readily suggests itself. But if so,
this virulence is capable of very rapid changes. We have seen a case
of maculo-anæsthetic leprosy, which probably arose by inoculation from
a very severe case of nodular leprosy, since the patient some years
before the outbreak of the disease had for a long time shared the bed
of a nodular leper. In this case the virulence of the bacilli must
have been at once diminished on their inoculation on another organism.
And since it also happens that a maculo-anæsthetic case may on a fresh
eruption become nodular, the bacilli must be able by cultivation in
the organism to re-acquire their power. Both are possible, but the
virulence of the bacilli seems to depend, not so much on any constant
character of their own, as on the soil in which they live.

Now it is a remarkable fact that in certain regions in Norway the
nodular form predominates; in others the maculo-anæsthetic does not
indeed predominate, but is present almost as frequently as the nodular.
The maculo-anæsthetic cases are more numerous in the eastern districts,
where the climate is dry; the nodular in the western, along the coasts
where the climate is moist. And in this western division there is a
region where the climate is not nearly so moist as in the division
generally, and here the proportion of maculo-anæsthetic cases is
distinctly higher, as may be seen by referring to TABLE III, page 144.

Sogn lies in Nordre Bergenhus, and is an inland fjord with a rather
dry climate. Söndfjord and Nordfjord lie nearer the coast, and have,
especially the former, very damp climates.

We have already noted that the leprous nodes are most frequently found
on the exposed parts of the skin, and it is quite possible that the
form is determined by climatic influences.

As the TABLE shows, males are more affected than the opposite sex, and
this too may depend on climatic influences.

It is also possible that the bacilli always possess the same virulence,
and that it is solely dependant on the soil in which they live, whether
they multiply freely or no. But it is impossible to say anything
definite on this, so long as we are unable to cultivate the bacillus,
and so long as we can only refer to the conditions in Norway; and
nowhere else have we such definite statistics of the disease and its
form as to justify us in drawing any conclusions.

We must, therefore, for the present leave in suspense this most
important and interesting question of the virulence of the Lepra
bacillus, since we possess no experimental proof of any attenuation.




CHAPTER VI.

DIAGNOSIS AND PROGNOSIS.


DIAGNOSIS.--In view of the description which we have given of the two
forms of the disease, the diagnosis is usually accompanied by little
difficulty. We have, however, noted above how a case of tubercular
Leprosy, with subcutaneous nodules only, was overlooked by a doctor
well acquainted with the disease; and we have occasionally seen, in
the country, people described by the doctors as leprous who were not
so. And, on the other hand, we ourselves were once in doubt as to the
diagnosis in a tuberous case, since all the nodules were exceptionally
small, and presented no characteristic appearance. But the doubt was
readily dispelled by the excision of a nodule and the recognition
of the bacillus. In the diagnosis of the maculo-anæsthetic cases,
one is more frequently in doubt, since the maculæ have not always a
characteristic appearance; sometimes they closely resemble psoriasis,
and in such cases the excision and microscopical examination of a
portion might clear away doubt. This we have never needed to do, since
the swelling of the lymphatic glands, or a thorough investigation
of the sense of touch, have always been sufficient to establish a
diagnosis. Even in comparatively, recent cases there may almost always
be detected some loss of sensation in the fingers and toes; sometimes
it is first evident on the wrists or back of the feet. For this
investigation one must either use callipers, or very slight stroking,
since deeper _pressure_ can be at once perceived. As a rule, the
maculæ themselves are somewhat anæsthetic. We recollect once seeing a
syphilitic eruption exactly resembling the leprous maculæ, but here the
history cleared up the diagnosis.

Maculo-anæsthetic Leprosy may in its later stages be confounded with
syringo-myelia, as Charcot has already noted in giving the points of
distinction between the two conditions. If the maculæ are no longer
present, careful investigation will often enable one to recognise their
previous presence by finding areas of skin, especially on the upper
arms, the back, the thighs and calves, which are somewhat paler than
the surrounding skin, and in which sensation is somewhat blunted. We
have thus frequently recognised the previous presence of maculæ in
patients who themselves knew nothing of them. Zambaco Pasha has stated
that certainly many of the cases described in France as syringo-myelia
and Morvan’s disease are cases of Leprosy; that Leprosy in this form
still exists in Brittany; and further, that he has there found some
cases of nodular Leprosy. It is remarkable that in these last cases,
where the proof would have been so easy, he has not demonstrated the
Lepra bacillus. From the drawings which he gives in the _Annales de
Dermatol. et de Syphil._ (T. III., Nr. 12), some of the cases can
scarcely be regarded as Leprosy, since on the hands with mutilated
fingers, no muscular atrophy can be noted; but in others there is
distinct atrophy, and these may very well be leprous, the more as
Pitres has published in the _Gaz. des hôp._ 1892, a case diagnosed as
syringo-myelia in which Lepra bacilli were demonstrated in an excised
portion of the ulnar nerve. It is unfortunate that Zambaco Pasha did
not demonstrate the remains of previous maculæ, which would probably
have been possible in some cases, were they really cases of Leprosy.
According to the rich experience of Dr. Danielssen and our own, it
must be admitted that a skin eruption is never absent in true cases of
Leprosy. With multiple neuritis from some other cause, it is, with a
good history and careful examination, not possible to confuse Leprosy;
and the same is true of progressive spinal muscular atrophy, where
there is no disturbance of sensation.

PROGNOSIS.--The prognosis is very different in the two forms. As
we have already stated, both forms may recover, since all leprous
products may disappear without any fresh ones appearing. _In nodular
cases this is a very rare exception, while it is the rule in the
maculo-anæsthetic._ Recurrent outbreaks are almost invariable in
nodular cases, and in them, too, nephritis is an almost constant
occurrence. Patients rarely live more than eight or nine years after
the definite outbreak of the disease. As already remarked, we cannot
state that Leprosy of itself is responsible for the end; we are rather
inclined to regard the nephritis and other complications as the direct
cause of death. The patients usually die long before the disease has
run its course. But in the maculo-anæsthetic form the cure of the
Leprosy is almost invariably the result. What remains, however, after
the cure of the leprosy, is very different. We have occasionally a
complete subject with vigour and good health, but usually only a
miserable rudiment of a human being, with more or less paralysed and
deformed hands and feet, with unclosable eyes, of which the lower part
of the cornea is opaque, and from which the tears run down over the
cheeks, and with paralysed facial muscles unable to close the mouth, so
that the saliva constantly dribbles from it. Such cases may, however,
live long and reach great ages, if under such circumstances this can be
looked upon as any advantage. They die usually from some intercurrent
disease.




CHAPTER VII.

ETIOLOGY.


There is hardly anything on earth, or between it and heaven, which has
not been regarded as the cause of Leprosy; and this is but natural
since the less one knows, the more actively does his imagination work.
And since all that was known of Leprosy was that it was a loathsome
disease, search was made everywhere for a cause. We will not linger
over the older literature of Leprosy. That may be found fully dealt
with in Danielssen and Boeck’s _Traité de la Spedalskhed_ and in
Hirsch’s _Geographical Pathology_.

Only after the work of Danielssen and Boeck can one say that Leprosy
entered the ranks of the scientifically investigated diseases. At
that time, in 1840, when they commenced their investigations, Humoral
Pathology held the field. Most diseases were ascribed to changes in
the blood, and they therefore endeavoured to establish that there was
in lepers a change in the blood which they regarded as the cause of
the disease symptoms, especially the node formation. These changes
in the blood they believed were caused by unfavourable conditions of
living, and as they were not able to find any convincing evidence of
the power of infection of the disease but several of its limitations to
certain families, they drew the conclusion that Lepra, as they called
it, might appear spontaneously, that is to say, that the sanguineous
dyscrasia which led to leprosy could be developed under unfavourable
conditions of life, but that it was in most cases hereditary. It must,
however, be noted that Danielssen always regarded Leprosy as a specific
disease, described it as such, and sought for a specific cause, and
the fact that he did not find it must be ascribed to the circumstance
that microscopical technique and microscopical aids, especially the
immersion lens, were at that time either insufficiently developed, or
not yet discovered. The teaching of Danielssen and Boeck was everywhere
adopted, especially their view of the heredity of the disease. The fish
diet and damp cold theories are only attempts to explain the so-called
spontaneous development of the disease, and they are founded on the
fact that Leprosy is chiefly present in littoral districts and on
islands.

Of other Norwegian investigators, the late Dr. Hjorth held the view
that Leprosy could not be ascribed to a specific cause, and that it
was certainly not hereditary. Dr. Holmsen regarded it as a specific
miasmatic and non-hereditary disease, and finally Prof. Lochmann stated
that it was specific, contagious, and hereditary. While Danielssen
and Boeck always required a leprous ancestor in order to recognise a
case as hereditary, and when this was not forthcoming, found in the
presence of the disease in other branches of the family, proof of its
heredity, Biedenkap, as he was unable in many of his cases to determine
the existence of leprous ancestors, widened the definition of heredity
by assuming that unfavourable conditions of life might produce in the
organism conditions which became hereditary, and showed themselves in
later generations as leprosy. In the year 1869, Dr. Drognat-Landré
published a book with the title, _De la contagion seule cause de la
propagation de la lépre_, in which he sought to prove that heredity had
nothing to do with the spread of Leprosy. That is, according to our
view, the right standpoint, as we shall endeavour to demonstrate.

As is seen from the above short summary of the views of Norwegian
investigators, some maintain the non-specific origin and heredity of
the disease; one only, the non-specific origin; one a specific cause
and no heredity; and finally, one a specific cause, contagiousness and
heredity.

It is rather remarkable that supporters both of the specific and the
non-specific origin of the disease should regard it as hereditary.
It apparently struck none of them that possibly the specificity of
a disease, that is, its development through the action of a poison,
might be incompatible with heredity. Since the discovery of the
Lepra bacillus and its recognition in all leprous products, it is
now everywhere admitted that it is the cause of the disease, and it
would therefore be superfluous to indicate which of all the symptoms
of the disease point to its specific nature. All this was shown in a
communication made by one of us to the Copenhagen Congress in 1884.
We start then from the assumption that Leprosy is a disease caused by
the Lepra bacillus, although it is as yet not strictly scientifically
proved, since inoculation on man and animals has not been definitely
successful.

The question as to heredity now is, Can the lepra bacillus be conveyed
by heredity. This is Baumgarten’s view; he holds that both Tuberculosis
and Leprosy are thus spread, that the bacilli of both diseases may be
transferred to the children and there remain dormant, but that they
can thence be conveyed to another generation, and from it to a fourth,
fifth, etc. generation, and then in the third, fourth, etc. generation
become once more active and cause the disease. We see at once that
this is only a modification of Biedenkap’s heredity, a peculiarity of
the organism which finally becomes evident as Leprosy. In place of
his undiscovered peculiarity, we have undiscovered latent bacilli.
Baumgarten’s view is therefore only a hypothesis for the explanation of
the origin of the two diseases. The hypothesis may be tested from two
points of view: first, we may sift it theoretically; and secondly, we
may investigate whether it can explain the distribution of the disease.

We must first endeavour to make clear _what heredity is_. As a matter
of fact we do not know; we are familiar only with a series of phenomena
which we call heredity, just as we have a series of phenomena which
we ascribe to the force of gravity, without knowing what gravity or
its force actually is. If we consider only the phenomena of heredity,
which are nowhere so completely and clearly put together as in Darwin’s
works, we find that he presents so-called laws of heredity, that is,
he has noted the most frequent phenomena of heredity, and thence
deduced a law. If the phenomena in the conveyance of a disease to one’s
descendants are to be called heredity, they must correspond with the
rest of the phenomena of heredity. And looked at thus, we know of no
specific disease which can be called hereditary. The conditions which
are hereditary are all anatomical and physiological peculiarities of
the organism. A bacillus which is living in the organism cannot be
regarded as one of its anatomical or physiological peculiarities; it
is a parasite. Now it is beyond doubt that parasites may be conveyed
from parents to children. Such are the _Achorion Schönleini_, and
the _Acarus Scabiei_. But this is no hereditary communication, it is
simply a present from the parent to his child. But, it is objected,
if the parasite is conveyed through the organs of generation during
copulation, then it is no longer a present or an inoculation, it
becomes hereditary. This appears to us a remarkable argument, that
conveyance by means of the organs of generation can change the nature
of the parasite and convert it into an anatomical constituent of the
organism of parent or child. A parasite remains always a parasite, and
since its conveyance from one adult to another is called infection, we
cannot comprehend why its conveyance to an ovum or a fœtus should be
indicated by another name. Were Baumgarten’s hypothesis correct, it
should certainly be called a hypothesis of latent infection, and not
a hypothesis of heredity. We said above that we knew of no specific
disease which was hereditary. To this it will naturally be objected
that syphilis is a typically hereditary disease. But we reply that
syphilis is a disease communicable to children, but that it is not
hereditary, and in order to maintain this statement we only need
to place in parallel the phenomena of the conveyance of hereditary
peculiarities and those of the communication of syphilis to children,
in order to make it perfectly clear how different the two methods are.

 CONVEYANCE OF HEREDITARY                   CONVEYANCE OF SYPHILIS
      PECULIARITIES.                             TO CHILDREN.

 1.--The hereditary peculiarity
 is usually limited to one
 sex, so that the male communicates         Not the case in syphilitic
 his peculiarities to                       children.
 his male descendants, and the
 female hers to the female.

 2.--Very often, possibly
 always, the appearance of                  In the communication of
 the hereditary peculiarity is              syphilis to children this is
 limited to a definite age.                 unknown.

 3.--Atavismus, or the overleaping
 of one or several                          Never known.
 generations of the heredity
 is very frequent.

Anyone who will maintain that these two forms of conveyance are the
same, and both hereditary, must evidently sacrifice facts.

We hold then, that a specific disease may be conveyed to the children,
but that it is never hereditary; the communication is by infection.

And since we regard leprosy as a specific disease we hold that it
cannot be hereditary. There remains, however, the further question
whether it can be conveyed to descendants by latent germinative
infection. This cannot _a priori_ be denied, although we have no
right to assume it from our knowledge of the lepra bacillus and of
the occurrence of the disease. We have indeed sought above to point
out the possibility that the lepra bacillus is attenuated in the
maculo-anæsthetic form of the disease; but we know of no phenomenon
which would allow us to assume that the bacillus could occasionally
become quite innocuous, and call forth _no_ symptoms of disease.

All this, however, proves nothing against the hypothesis; and it is
always a dangerous thing to use a simple absence of knowledge either to
contradict or to found a hypothesis.

But we think we can supply an almost incontrovertible proof that
Baumgarten’s hypothesis is wrong. It is well known that the Belgian
Father Damien became a leper in the Sandwich islands. If the Father
was of pure Belgian ancestry, and his disease was caused by latent
hereditary bacilli, then these bacilli must have been at least several
hundred years old, unless one assumes that one of his nearer ancestors
had had connection with a leper, and that in this way the Father had
acquired his bacilli. Against this is the explanation that the Father
who tended the lepers on Molokai, with self-sacrificing love, was,
through some want of care or caution, infected as he went in and out
among the lepers. The choice between the two explanations does not
appear to us a difficult one.

The view of the non-communication of leprosy by latent bacilli is
further strengthened by the fact that there are places in Norway where
many descendants of lepers live without one single one of them becoming
leprous, as for example, in the town of Bergen where the descendants
of lepers may certainly be numbered by thousands; and further, we
have demonstrated by our investigations in North America, that of the
numerous descendants of Norwegian lepers there, not one has developed
the disease. But since about one hundred and seventy leprous Norwegians
have emigrated to America, it may possibly be that the disease is
spread by infection. There are indeed cases in America which have
possibly arisen from infection, but they are not sufficiently definite
to serve as arguments for its contagion. But even if leprosy be a
contagious disease, one can easily understand how it should spread
little, or not at all, in North America, when one compares the social
condition and especially the cleanliness there with that in Norway, and
probably especially with that of the districts in which leprosy is most
prevalent. In North America the dwelling houses are roomy, so that the
lepers whom we saw there had usually their own room, or at least their
own bed; and everywhere, even among the Norwegians, great cleanliness
is observed. And this is, according to our view, sufficient isolation
in order, in most cases, to prevent the spread of the disease.

That leprosy is really contagious is primarily evident from its nature
as a bacillary disease. No one has been able to demonstrate the
presence of the bacillus outside the human body, so that we may abandon
the idea of a miasmatic origin.

Unfortunately, all attempts to inoculate animals have failed. The now
old experiments of Neisser and Damsch, as well as our own, we may pass
over. We dealt with them in our Copenhagen communication. Since then
Melcher and Ortmann believe that they have communicated the disease to
rabbits. Dr. Ortmann has kindly sent us preparations from the infected
rabbits, and on close examination of them we regret to say that we
lost our faith in the leprous nature of this affection of rabbits. We
found both caseous degeneration and myelo-plaques in the preparation,
which, as we have noted, we have never found in leprosy. At the same
time the affection does not look exactly like tubercle, and it is
possible that in rabbits leprosy appears otherwise than in man. But we
may note that Veterinary Surgeon Nielsen has, here in Bergen, observed
a disease in mice, which shows a close resemblance to Ortmann’s rabbit
leprosy. Inoculated on a rabbit, the disease appeared with new growths
in the cœcum, just like Ortmann’s rabbit leprosy. These new growths
had certainly more resemblance to tuberculosis; but there were in them,
at many places around the vessels, cells, crammed full of bacilli.
Nielsen’s investigations are not yet concluded, but it is possible that
the disease is one of animals as yet unknown, which Melcher and Ortmann
have by chance conveyed to their rabbits. All the inoculations of
leprosy on rabbits which Dr. P. F. Holst made in the laboratory of the
Lungegaards Hospital were unsuccessful; not one of the infected animals
became leprous.

Although, as we have stated above, the lepra bacillus has never been
found outside the human body, this might possibly be dependent on
insufficient search, and it might be possible that the old view at
present maintained by Hutchinson is the right one, viz., that leprosy
is caused by the eating of putrifying fish, or that the contention of
Holmsen that leprosy is a miasmatic disease, is correct.

Against Hutchinson’s hypothesis there is in the first place the fact
that we have never succeeded in cultivating the bacillus, which, if the
bacillus lived as a saprophyte on decaying fish, would be a very simple
matter. And there are, secondly, places where the inhabitants certainly
and frequently enjoy decaying fish without the disease appearing. And
thirdly, there are many places authoritatively indicated where leprosy
is present, and where no fish is ever eaten. For his hypothesis of
the miasmatic origin, Holmsen can only bring forward the fact that
the disease is often limited to certain districts. This is certainly
correct, but this endemic appearance of leprosy may be as readily
explained by infection, while the localities affected do not give the
slightest support to the assumption of a miasma. Such areas are found
here in Norway, both on the bare cliffs, on the coast, in the valleys,
and on the mountains.

There is, therefore, no other course open to us but to assume the
infectiousness of the disease, and thus the spread of leprosy
is readily understood; while by the assumption of heredity, or
Baumgarten’s latent germinative infection, it remains absolutely
inexplicable. These two last causes are to our thinking absolutely
proved to be non-existent by the case of Father Damien; by the results
of our investigations in North America; and by the diminution of the
disease in the descendants of lepers in the Norwegian towns.

But _direct proofs_ of its contagiousness may also be obtained. Such
are given by Drognat-Landré in his book, and also by many other
observers. Norway can supply many proofs; but against these it can
always be urged that it is impossible to exclude the possibility of
inheritance on account of the widespread nature of the disease. But we
think we can supply from Norway a still better proof in the shape of
the gradual diminution of the disease during the last thirty-five to
forty years.

Up to 1856 leprosy probably increased in Norway; we cannot speak more
definitely, as previous to that year there was no exact or sufficient
enumeration of the lepers. But we have grounds for believing that we
have obtained, by means of the yearly census begun in 1856, a pretty
exact knowledge of the number of new cases in the years 1851-55,
and this shows that the number is considerable, and almost exactly
corresponds with the number of new cases in the next five years,
1856-60. This, we think, indicates that the total number of lepers in
the two quinquenniums was pretty much the same. Now we know that there
were in Norway in 1856 over 2800 lepers. The number was estimated
in 1836 at 659, and in 1845 at 1122. According to this estimate a
considerable increase had taken place. We can, however, with certainty
say that the numbers for 1836 and 1845 are too low. In the first place,
the enumeration was not undertaken by medical men, and secondly, even
now, there are many lepers overlooked at every enumeration, or, to
speak more correctly, they are not discovered because the patients
conceal their condition. But that the number of those overlooked in
the years 1836 and 1845 can have been so great as the difference
between the numbers for those years and that for 1856 is scarcely
credible, and it therefore appears probable that the number of lepers
in Norway increased during the first half of the century.

In the year 1856 the first Leper Asylum was opened in Bergen.
Previously to this we had in Bergen the St. Georg and Lungegaard’s
Hospitals, which together served for 200 patients. In Molde there was
also a small hospital, for lepers, so that altogether in the year 1856
there were about 235 lepers in hospital. In 1861 were opened two new
asylums, one in Molde, the other in Trondhjem (Drontheim), and as is
seen in TABLE IV (p. 145), since that time a large number of lepers
have been admitted to these institutions.

We may regard the numbers in this TABLE up to 1885 as accurate; for
the later years corrections will have to be made from the later
enumerations, which may detect older, concealed cases. But these can
only affect the figures to a limited degree.

If we consider the TABLE closely, we see that in the first quinquennium
(1856-60) the total number of lepers is 76 less, while those in their
own homes are 380 less; during this period 585 lepers were admitted
to the asylums. The number of lepers as a whole, then, was not much
reduced, but at the end of the period there were 380 lepers fewer
at home, or, in other words, there were among the people 380 fewer
sources of infection, and to this we ascribe it that while the number
of new cases was 1,148 in the years 1856-60, it fell in the years
1861-65 to 1,028. The mortality of the year 1856 we do not know; in
the four following years 981 died--668 at home, in the asylums 313. If
we assume that there died at home as many in 1856 as in 1857, viz.,
230, then the number of deaths at home during the quinquennium would
have amounted to 898, and the whole mortality, adding the 313 who
died in the asylums, would have been 1,211--only 109 more than the
new cases. But one must not so reckon. There died, especially in the
early days, a much larger proportion in the asylums than outside; and
it is evident, secondly, when one observes the figures in a district
from which at the commencement only very few cases were sent to the
asylum, that the new cases are much more numerous than the deaths. In
Nordmoere, for example, the number of new cases from 1856-60, was 81;
that of deaths, 46; only 14 were sent to the asylums, and the disease
increased during the quinquennium, the cases rising from 105 to 119.
One finds the same thing in Soendmoere--new cases 104, deaths 42, sent
to asylums 28; number of cases in 1856, 178; in 1860, 195. In these
two districts, then, the disease was evidently on the increase, and
this would probably have been the case throughout the country, had
many cases not been removed from their homes to the asylums; as, for
example, in Soendfjord. Here there were, in 1856-60, 214 new cases,
116 deaths, 211 sent to the asylums; number of cases 1856, 431; 1860,
306. If we examine in this way the numbers in the different districts,
we find everywhere that decrease of the disease depends on the numbers
isolated in the asylums. Where isolation was insufficient or absent,
there was no decrease, but either the numbers increased or remained
stationary; where, on the contrary, isolation was thorough, the
decrease was invariable. This can only be explained in one way, viz.,
that isolation is the cause of the decrease, and isolation can only
have effected improvement by removing from the homes of the people the
sources of infection. Further, during the next five years, the number
of new cases in those districts where isolation was good continued to
sink; where there was none, or it was insufficient, the numbers either
rose or remained almost stationary. We will once more compare Nordmoere
with Soendfjord. In Nordmoere, in 1856-60, 81 new cases, 14 sent to the
asylum; 1861-65, 88 new cases. In Soendfjord, 1856-60, 214 new cases,
211 sent into asylums; 1861-65, 146 new cases.

We consider it superfluous to point out further how the isolation
of the patients has caused the decrease of Leprosy in Norway. It is
not possible to explain the action of isolation by the elimination
of heredity; the time is too short for that. The only one possible
solution is that which we have given, and therefore we regard this
decrease of Leprosy in Norway following on isolation as the best proof
of the contagiousness of Leprosy. Leprosy is, then, according to our
view, a contagious disease, and only contagious, not hereditary.

How Leprosy is “caught,” we do not know, but we think it is probably
by inoculation; and the nodular form must be more dangerous than the
maculo-anæsthetic. This last statement seems to be confirmed by the
fact, that in Sogn, where 56.6 per cent. of the cases are nodular and
43.4 per cent. maculo-anæsthetic, the increase varies between 8. and
10.8 per cent., while in Soendfjord, with 72.6 per cent. nodular, and
27.4 per cent. maculo-anæsthetic, it is between 14.4 per cent. and
19.5 per cent. In the nodular form there are incomparably more bacilli
than in the maculo-anæsthetic, and in the latter there is no discharge
containing bacilli, which in the former is almost always present. It
is not improbable that Leprosy may be conveyed by the clothes. We know
of one case in which a young man became affected one year after he
had worn a pair of old drawers given him by a leper. The same thing
happened to another young man who wore several pairs of his leprous
father’s stockings.

Although we are not acquainted with the spores of the Lepra bacillus,
it is quite conceivable that the bacilli are spore bearing.
Unfortunately, we know of no method of determining whether the bacilli
are alive or dead, and therefore Arning’s observation of the bacilli in
the fæces does not decide the question as to whether the bacilli can
live for any time outside the body, even admitting that the bacilli
which Arning found were actually Lepra bacilli.

After completing this work I received “The Recrudescence of Leprosy
and its Causation,” by William Tebb. The author seeks to prove that
leprosy is everywhere on the increase as the result of the introduction
of vaccination. The book as a whole is directed against vaccination
as dangerous. Distinct proofs for his contention that leprosy may be
conveyed by vaccination from arm to arm, the author, to our thinking,
does not supply. Since Dr. Arning found lepra-bacilli in the contents
of vaccine vesicles in lepers, the possibility of the communication in
this way can scarcely be denied. But that it can be frequent, I cannot
possibly believe. In Norway, vaccination has been compulsory during
all those years in which leprosy has steadily diminished. In 1891 I
put the question to all those doctors in Norway who had anything to do
with leprosy, whether they had ever met in their practice with a case
which could be ascribed to vaccination. Not a single one had observed
such a case. And yet, here in Norway, lymph must often be taken from
the children of leprous families. But since leprosy is very rare in
children, it is evident that leprosy cannot be conveyed in this way.
That vaccine vesicles in the non-leprous members of leprous families
contain lepra-bacilli is incredible.




CHAPTER VIII.

TREATMENT.


Since many cases of Leprosy terminate in cure by the disintegration
and elimination of the bacilli, one might imagine that it would be a
tolerably easy task to find a suitable treatment for the disease. But
this is far from being the case. Treatment of Leprosy has been carried
out from time immemorial. In the Bible there is little concerning any
treatment which was regularly applied in Leprosy; the disease being
apparently regarded as beyond human power. Later, all possible and, we
may say, impossible remedies, such as the teeth of elephants, the flesh
of crocodiles and serpents, the fat of panthers, lions and bears, and
so on, were applied. In mediæval times, the same class of remedies was
used along with religious incantations.

In the eighteenth century, Schilling tells us he treated leprosy with
success. For the first three months he ordered a rather sparing diet,
consisting of bread, vegetables and soup. The real treatment began
with purgatives, “not mineral ones, because these are dangerous for
lepers, and often produce dangerous diarrhœa,” and was followed by
warm baths, “with circumspection, when the disease is far advanced,
because they produce palpitation of the heart, convulsions and fainting
fits.” In addition to advising frequent exercise in the open air,
Schilling regarded it as important to dilute the diseased humours by
large quantities of purifying fluids, of which he used first emollient
decoctions, and later, powerful sudorific ones. As mild ones he used
barley water, infusions of herbs, Agrimony, Hedera terrestris, Fumaria,
Veronica, etc., to which were sometimes added other softening and
purgative remedies, such as Malva, Parietaria, Senna and Rhubarb.

Of these the patients took, for six weeks, 3 to 4 litres daily. He
then gave powerful resolvents and sudorifics, as Saponaria, Zedoaria,
Sassafras, Juniper, Fol. Scolopendrii, herb. Cardui benedicti, Pareira
brava, etc. The more the patient could take, the more rapid and
complete, according to Schilling, was the cure. Rich food and good
wine might be given. During the treatment the patient had to guard
himself from cold air. After three months the patient was bled, as much
blood being taken as his strength would allow. The external remedies
which were used when there were putrid ulcerations, and when fingers
and toes commenced to fall off, were tincture of aloes, myrrh, and
succini, which were dropped on lint and applied twice a day. Both the
pharmaceutical and the dietetic remedies were to be persevered with
until definite signs of cure were manifest, and the treatment was to be
continued for many months after apparent recovery. Many years ago this
method of treatment was carried out at the Lungegaard’s hospital, but
without success.

We shall next mention all the specific remedies which have been
recommended and have acquired any reputation as effective.

_Madar_ (Mudar) is one of the oldest. It is got from the Indian plant,
Caloptris gigantea (_Asclepias gigantea_). Only the powdered bark of
the root was used. Some of it was sent from India to the Lungegaard’s
hospital, and was given in large doses to many lepers. The effect was
absolutely _nil_; one might just as well have given them flour.

Dr. George Watt enumerates the following plants of which the oils have
been used in India in leprosy:--(1) Albizzea Libbek, (2) Anacardium
occidentale, (3) Gynometra ramiflora, (4) Dipterocarpus turbinatus, (5)
Gynocardia odorata, (6) Hydnocarpus Wightoni, (7) Hydnocarpus venenata,
(8) Pongania glabra, (9) Psoralea corylifolia, (10) Sunocarpus
anacardium, (11) Arachis hypogæa. Of these, only a few merit more
particular mention; the others have been mostly merely popular remedies.

_Cashew-nut Oil_, from Anacardium occidentale, Linn., Cassuvium
pomiferum, Lamk, a large tree very common in the West Indies. The oil
is found in the pericarp, and is extracted by ether, which, after being
evaporated in open vessels, leaves a thick, brownish black oil--the
Cashew-nut oil. This is the oil with which the French physician, Dr.
Beauperthuy, in Cumana, Venezuela, claimed to have cured leprosy. An
English physician, Dr. Bakewell, who had investigated the treatment
of Dr. Beauperthuy, sent a report to both houses of parliament on
the beneficial effects of the treatment, and it thus attracted much
notice. Dr. Beauperthuy’s method of treatment was the following: good
nourishing diet, good hygienic surroundings, frequent warm baths
followed by the inunction of olive oil, and internally 1/15 to 1/20
of a grain of bichloride of mercury twice daily, or, when this was
contra-indicated, 10 to 20 grs. of carbonate of soda. As external
remedies, which Beauperthuy regarded as the most important, he applied
different liniments, such as tincture of iodine, to which were added
potash lye, olive oil, and balsam of copaiba mixed with yolk of
eggs. These liniments he principally applied where herpetic or other
eruptions complicated the leprosy, and to the specific eruptions he
applied solutions of nitrate of silver or sulphate of copper, but
especially Cashew-nut oil. In all this there is nothing new except
the oil; all the other remedies have been long, and still are
occasionally, used. In the Lungegaard’s hospital, the oil was tried on
five patients exactly according to the directions of Dr. Beauperthuy,
and after a trial of several months, the results were anything but
good. The oil induced irritation, redness, swelling and vesiculation;
the leprous tubers and patches remained unaltered, and in one case a
leprous eruption developed, probably produced by the irritation of the
oil. In Trinidad, too, the same results of the application of the oil
were seen, and Dr. Beauperthuy’s treatment has been given up.

Even before Dr. Beauperthuy’s remedy had lost its reputation, a new
specific remedy appeared in the East Indies, viz., _Gurjun oil_,
introduced by Surgeon-Major Dougall, of the Andaman Islands. The oil is
procured from several species of Dipterocarpus, principally D. lævis,
D. tuberatus, and D. trinervus. Dr. Dougall’s method of treatment was
the following: good nourishment, fresh air, and a mixture of gurjun
oil and lime water internally and externally. For internal use he
gave a mixture of equal parts of oil and lime water, which forms a
tolerably thick emulsion, 15 grains morning and evening. Externally,
he used an ointment of oil 1 part, and lime water 3 parts. With this
the patients rubbed the whole body for two hours both forenoon and
afternoon. The body was thus covered with a sticky layer, to which dust
and dirt adhered. To remove this, the patients rubbed themselves every
morning with dry earth, and afterwards took a bath in running water,
before again applying the oil. The prolonged rubbing he considered not
only beneficial to the skin, but useful as a gymnastic exercise. Of
twenty-four lepers whom he treated in this way for six months, all,
without exception, improved; all ulcerations healed without again
breaking down; and, what is most remarkable, the anæsthesia almost or
completely disappeared.

According to his description of the patients, some of them evidently
had syphilis, some chronic eczema, and some psoriasis. Their
ulcerations had been so neglected that flies laid eggs in them, and
it is little wonder that they healed under the cleanliness which Dr.
Dougall induced. That old anæsthesia should disappear within six
months, is, to any one who knows leprosy, absolutely incredible.

In the summer of 1887 the Lungegaard’s hospital got a sample of the
oil, and nine male lepers underwent Dr. Dougall’s treatment, the only
difference being that they took a warm bath instead of a bath in
running water, which Dr. Dougall probably ordered because he had no
bath-rooms at his disposal. Every morning and evening the patients
took 15 grains of the mixture of equal parts of oil and lime water. In
the forenoon, from 9 till 11, and in the evening from 5 till 7, they
rubbed each other in a room at a temperature of 26 to 28° R., with oil
1 part and lime water 3 parts. In the morning they rubbed themselves
with dry earth, and took a warm bath before re-applying the oil. The
treatment led to no results. In some of the patients the disease
advanced very little, but, nevertheless, the gurjun oil had no effect.
As leprosy, so far as we know, is the same disease in the East Indies
as in Norway, it was surprising that the gurjun oil should cure it in
the one place and not in the other. Later trials of the treatment in
India have had the same negative results as in Norway.

_Chaulmoogra_, which the medical department of Madras has used with
success, is the oil pressed from the seeds of Gynocardia odorata,
Lindl. Hydrocarpus odoratus, Lindl. The oil is given internally (2
grs. in an ounce of milk) twice daily, and externally, there is rubbed
in a mixture of oil 1 part, and olive oil 16 parts, followed some
hours after by a bath. We are told that the progress of the disease is
stopped by a persevering use of the oil. The skin becomes smoother and
more elastic, the patient becomes more energetic, the discolorations
disappear, and so too does the anæsthesia, either partly or completely.
Ulcerations heal, but promptly break down again. Besides the treatment,
a generous diet is given, especially vegetables, milk and meat; spices
and spirits are not allowed. Dr. Arjoon says that the tuberous form
heals more easily than the mixed leprosy, and that anæsthetic leprosy
is the most obstinate. When the disease is inherited there is no hope
of a cure, and it is only in early cases that a cure can be expected.
Further, he thinks that the permanence of the cure is doubtful.

In the Lungegaard’s hospital three tuberous and two anæsthetic patients
were treated with chaulmoogra oil. The treatment was continued from
eight months to a year, but the results were, as with the other
remedies, _nil_.

Father Etienne sent to the Lungegaard’s Hospital from Port of Spain,
Trinidad, a quantity of pills containing a vegetable, Hoang-nan, which
he had received from some missionaries in Ting-King. He had used the
pills for three years in leprosy with surprisingly good results. In
several patients all the external symptoms of the disease disappeared,
and he had good hopes of their complete cure. His report seeming
to guarantee the remedy, it was given a trial in the Lungegaard’s
Hospital. After prolonged use it proved to be absolutely useless, and,
since no more has been heard from him, Father Etienne has probably been
disappointed with his later results.

Father Damien also received from Ting-King a supply of pills for the
cure of leprosy, which were, no doubt, of the same nature. He found
them to consist of alum. sulph., pts. 1.5, Realgar 2.5, and Hoang-nan
2.5.

Hoang-nan belongs to the _Euphorbiaceæ;_ the cortex contains a powerful
poison which is the active remedy. At first Father Damien believed
the remedy to be of some benefit “to us poor lepers”--he was then a
leper--but further experience showed him that the remedy was, like so
many others, unsatisfactory.

The last remedy to be mentioned is one which once attracted much
notice, and on which the French academy allowed Dr. Gibert to write a
report. The remedy is _Assacou_ or _Ussacou_, Brazilian names of the
tree _Hura Braziliensis_, Martin, of the family _Euphorbiaceæ_. It is
considered very poisonous.

Several physicians in the West Indies have tried it, and amongst them
Dr. Maldur, who treated four lepers in Santa-Caza da Misericordia,
with, he believed, great benefit; other trials, however, failed, and
the remedy has been laid aside.

The foregoing reports of the results of the treatment of leprosy with
different specific remedies, are taken from the experience of the late
Dr. Danielssen, who spent half a century trying to cure leprosy, and we
shall now give some of the various methods of treatment he used.

Early in the development of bacteriological research, Dr. Danielssen
already suspected the bacterial nature of the disease, and began to use
germicides.

_Carbolic acid_ was given in solution, 8 grains to 8 ounces, 1
tablespoonful four times daily, and he went so far as to give 20 grains
to 8 ounces in the same way. Externally, he applied carbolic acid as an
ointment or a lotion. It was used by fifty-three lepers from three to
eighteen months, but had no effect on the disease.

_Creasote_ was used in 1838 by the late Dr. Hjort, and later by
Danielssen, without any good effect. Prof. Langerhans of Madeira, told
Dr. Danielssen that he had seen several lepers on Teneriffe, whom Dr.
Perez, at his suggestion, treated with creasote in increasing doses,
with good effect, and he therefore asked Dr. Danielssen to try it once
more. Consequently, creasote in pills (0.025 gr. in each pill) was
administered to five tuberous lepers, in an early stage of the disease.
They took the pills for six months without any effect on their leprosy.
Two of them took the pills for fifteen months, and as many as 20 pills
a day. The pills did neither good nor harm; their influence on leprosy
was _nil_.

In the early years of the Lungegaard’s hospital (1849-50) glacial
phosphoric acid was largely used without benefit.

_Phosphorus_ was given in doses of 2 to 3 milligrammes daily. After
some months it was given up because it caused indisposition and
destroyed the appetite, while the leprosy remained unaltered.

_Arsenic_ has been used by many physicians in the treatment of
leprosy. Dr. Danielssen tried it in the form of Fowler’s solution, and
the so-called Asiatic pills, in gradually increasing doses, but the
prolonged use of arsenic, instead of doing good, made the patients
worse, causing gastro-enteritis and emaciation. The emaciation caused
diminution in the size of the tubers, which has been regarded by many
physicians as an improvement; but this is a fallacy, for, when the
patient regains his former good condition, the nodules regain their
former size.

_Ichthyol_ was tried internally in the form of pills, 10 centigrammes
thrice daily, increased up to 2 grammes daily; but no benefit was
observed, although it was continued for almost a year.

From Dr. Englemann, in Kreuznach, Dr. Danielssen got a sample of
Kreuznach salt, and directions how to use it. The bath was prepared
thus: 3 lbs. of common salt, 4 lbs. of Kreuznach salt, 264 litres of
water. Temperature 35°C. After the lapse of a week the Kreuznach salt
was increased to 6 lbs., after a fortnight to 12 lbs., and after three
weeks to 16 lbs. The patient remained from one-and-a-half to two hours
in the bath, and no other medicine was taken. Forty-six baths were used
by five lepers, four tuberous, and one anæsthetic. At the same time,
a young man with a recent eruption of leprosy was sent to Kreuznach
to take the baths under Dr. Englemann’s directions. After a year Dr.
Danielssen saw him again, when no improvement was to be observed, and
the same was the result in the cases treated here.

_Mercury_ in its different combinations has been tried internally and
externally, but instead of producing any good effect it has rather made
the condition of the patient worse.

_Iodine_ has been used as iodide of potassium, and externally as
tincture of iodine and iodine ointment. At the beginning of his studies
in leprosy Dr. Danielssen had great confidence in iodine, but he soon
learned what a very dangerous remedy it was in this disease. Even small
doses of iodine produce new eruptions of leprous tubers or patches,
and Dr. Danielssen therefore ultimately used it as a test in cases of
apparent cure. When a patient was considered cured, he gave him iodide
of potassium, and if no new eruption developed, the cure was considered
complete.

Some years ago Dr. Unna, of Hamburg, claimed to have cured three
lepers, and Dr. Danielssen, using Unna’s method, cured one. The
treatment is the following: Internally, pills of ichthyol in increasing
doses; externally, the rubbing of arms and legs morning and evening
with an ointment of 10 per cent. pyrogallic acid in lanolin, and
the breast, back, neck, and cheeks, with 10 per cent. chrysarobin
in lanolin; the covering of the forehead and chin with a plaster
consisting of chrysarobin, salicylic acid, and creasote, which is
changed every second or third day. This treatment was continued from
December 16th, till January 11th; then followed a few days of plain
baths, and then the same treatment again. In the Lungegaard’s hospital
Dr. Unna’s treatment was tried by thirteen lepers, five nodular, four
anæsthetic, and four mixed. The results of the treatment were not so
satisfactory as in Dr. Unnas hands, and there was certainly no question
of a cure.

_Koch’s tuberculin_ was administered to five anæsthetic, three
tuberous, and three mixed cases, as a rule, daily, from January 8th to
May 8th. The dose at the commencement was 1 milligramme, and in several
cases as much as 320 milligrammes were finally injected. The injections
were made, sometimes daily, sometimes at intervals of a few days,
according to the degree of reaction which followed the injections.
In some cases the injections had to be stopped very soon, because
they produced fresh leprous eruptions; and in one case bacilli were
found in the blood. It seemed as if the tuberculin had set the bacilli
afloat. We came to the following general conclusions:--(1) Tuberculin
administered to lepers produces a general and local reaction, usually
forty-six hours after the injection, seldom after twelve hours, and
very seldom after two to three days. The local reaction becomes evident
later. (2) These reactions do not beneficially influence the leprosy,
they rather aggravate the disease by causing fresh eruptions just as
iodide does. (3) Tuberculin does not kill the lepra bacillus. (4)
Immunity against tuberculin can be attained, but this immunity does not
influence the progress of leprosy.

Dr. Carreau, in Guadaloupe, treated a leper with _chlorate of
potassium_, he believed with great benefit; he gave the remedy in
enormous doses. Dr. Hjort had, already, in 1838-39 tried this remedy
without effect. Dr. Beaven-Rake has also tried the remedy according to
Dr. Carreau’s directions, but also without result. Dr. Danielssen, too,
tried it, but without any benefit.

During the last few years the following remedies have been tried in
the Lungegaard’s hospital: Hydroxylamin, Europhen, Naphthol, Salol,
Methylene blue, Aristol.

_Hydroxylamin_ forms colourless crystals, easily soluble in alcohol
and glycerine. It is decidedly poisonous, and is, according to some
authors, a more powerful reducing agent than chrysarobin or pyrogallic
acid; 2 to 5 hydroxylamin to 20 glycerine and 80 alcohol, was painted
on the patches of four maculo-anæsthetic lepers. In two of them there
developed, after the painting, an erythema, during the persistence of
which the painting was discontinued. The painting was continued for two
months, and then a 2 per cent. hydroxylamin ointment was applied, but
as no amelioration could be noted after four or five months, the remedy
was laid aside. In four tuberous patients the painting could only be
continued for two or three days, because the spots re-acted severely,
grew red and painful, and vesicles formed. The tubers somewhat
diminished, but otherwise the condition remained unaltered.

_Europhen_ has some resemblance to iodoform, but gives up its iodine
less readily. It is a fine yellow powder, insoluble in water, but
soluble in alcohol, ether, chloroform, and oil. A solution in oil was
used for hypodermic injections: at first 0.015 europhen was injected,
and after a month 0.025. At the end of another month an eruption
developed in one of the patients; in the others no effects were
evident, and thereupon 0.030 was injected. After three weeks an iodine
eczema developed in three of the patients, and a leprous eruption in
another, and consequently no further trials were made. Dr. Julius
Goldschmidt of Madeira, has also used this remedy, and considers one of
his patients as almost cured, while four others remain unchanged.

_Aristol_ was tried by three patients, partly internally, dissolved in
ether, and partly externally, in the form of ointment; the effect was
the same as after the use of iodide of potassium, and it was stopped
after three weeks’ trial.

_Naphthol_ and _Salol_ were tried for a long time, but the effect was
almost _nil_. Salol has also been used by Dr. Lütz in the Sandwich
Islands, and by Surgeon Major Cook in Madras, but though some
amelioration in the condition of the patients has been noted, no case
has been cured.

_Methylene Blue_ was given to one tuberous patient, both internally
and hypodermically. The skin, especially the tubers, became deeply
blue, but a microscopical examination showed the bacilli unaltered. The
treatment was continued from May 20, 1891 till January 30, 1892. Some
tubers diminished a little, but most of them became larger, so that the
disease as a whole grew worse.

_Nerve stretching_ was first tried by Dr. Gerald Bamfert, who stated
that he had done the operation with success on an anæsthetic patient,
in whom both hands were atrophic and sensibility much diminished. The
ulnar nerve was stretched and incised longitudinally. The sensibility
in the right hand re-appeared immediately after the operation; and
after some days the muscular power was almost completely restored. In
three anæsthetic patients in the Lungegaard’s hospital the operation
was performed; the ulnar nerve was stretched and incised along a length
of three to four inches. All went well, only the anæsthesia remained
unchanged; neither sensibility nor muscular power was restored. Dr.
Beaven-Rake, who has done numerous nerve-stretchings in Trinidad, says,
“on the whole the results of nerve-stretching for anæsthesia cannot be
considered satisfactory.”

Dr. Beaven-Rake has also done the operation for pains in the limbs, for
which hypodermic injections of morphine have been successfully used in
the Lungegaard’s hospital.

_Electricity_, both faradic and galvanic, has been used for anæsthetic
leprosy, and electric baths, but no good effect has been attained.

Surgical measures are often needed. Section of the cornea, as
introduced by Dr. Boeckmann, in the case of tubers growing into it, has
already been mentioned, as has the operation of tarsoraphia interna in
ectropion of the lower eyelid. Iridectomy has often to be performed,
when the pupil has been obliterated by adhesions of the iris or by
exudation.

Tracheotomy is necessary when the larynx is occluded by leprous-growths
or by cicatrices.

Necrotomies should always be performed when there is necrosis of the
bones of the hands and feet. It is astonishing how well the wounds heal
in the anæsthetic parts, and patients are spared from long-standing
suppuration by the removal of the necrosed bones.

The best remedy for leprosy Dr. Danielssen found in his experience
to be _Salicylate of soda_. If the patients were badly nourished, he
first administered quinine, iron, cod-liver oil, and nutritious food,
and when the patient’s condition was satisfactory he gave 1.0 gramme
salicylate of soda four times daily, and for six months or a year the
dose was gradually increased. Its good effects were seen in both forms
of the disease. In the maculo-anæsthetic form the patches and the
less extensive anæsthesias slowly disappeared. In the tuberous form,
when not of too long duration and severity, the rapidity of progress
was diminished, and fresh eruptions were prevented. A complete cure
has, however, not been attained, unless, at the same time, there have
been applied regularly “cucurbita cruenta,” steam baths, alternating
with warm water and sea-water baths, exercise in the fresh air, good
hygienic surroundings, and good diet. From time to time irritants
were applied, such as, carbolic and salicylic acids, in the form of
fomentations and ointments. It is only in cases in the first six to
twenty-four months that a favourable issue can be hoped for. The
results of the treatment in the Lungegaard’s hospital are nothing to
boast of, but they show, according to Dr. Danielssen, that leprosy at
its commencement can be cured. In our opinion this is true, but with
the reservation that the cure is not due to the treatment, but is the
natural development of the disease. We have seen cases of leprosy, in
the country, both tuberous and maculo-anæsthetic, completely recover
without any treatment whatever. So far as we know, in most of the
patients discharged cured from the Lungegaard’s hospital the anæsthesia
has increased, which is in conformity with the general progress of
the disease, the nerve fibres continuing to undergo atrophy from the
pressure of the contracting inflammatory tissue in the nerve trunks, as
described above.

Treatment ought theoretically to be directed to the destruction of the
bacilli, and this is what Dr. Unna sought to attain by his reducing
remedies, pyrogallic acid, chrysarobin, etc.; but while Dr. Unna and
Dr. Deichmann succeeded in Hamburg, Dr. Danielssen had no success when
using the same remedies. Dr. Danielssen believed that the bacilli were
destroyed by salicylate of soda; but we fear that others will not
succeed with this same remedy.

As we are then, in our opinion, unable to destroy the bacilli with
remedies, either internal or external, it only remains to us to
prevent infection, and that can only be attained by isolation of those
affected. For this isolation no very costly measures are required.
From what we saw in North America in 1888, all that is wanted is
cleanliness, both personal, and in the household. But amongst the
people where leprosy prevails, it is almost impossible to get
sufficient cleanliness thoroughly enforced. We think, therefore, that
the best measures are those which have been taken in Norway, where the
lepers are isolated at their own request, and where the communities can
get rid of the disease, if they will, since the sanitary authorities
have the power to order the leper to live sufficiently isolated from
his family, and, if he cannot or will not assent to this, can compel
him to enter an asylum. At the same time, the doctrine of cleanliness
and isolation and the necessity of their observance in order to prevent
the spread of the disease, is constantly preached.

Since the state pays all the expenses of the lepers in the asylums,
their families are generally relieved by getting rid of the lepers,
who are almost invariably bad workers and unable to earn their living.

These measures are quite adequate in a democratic country like Norway,
where the communities have governed themselves since 1836, and the
results are most satisfactory, seeing that we had in 1856, 2833 lepers,
and at the end of 1890 only about 950, which number, when corrected,
will probably amount to about 1100.

Whether the same measures would be adequate in other countries where
leprosy prevails, we cannot of course say; it must depend on the social
condition of the community. But we are firmly convinced that isolation
_must_ be carried out in some appropriate fashion.




TABLES.




_TABLE I._

KEY:

 Column heading
 D -   Duration of disease in years

 Body of table
 A -   Amyloid
 F -   Fatty degeneration
 L -   Leprous
 N -   Normal
 NpA - Acute nephritis
 NpI - Interstitial nephritis
 NpP - Parenchymatous nephritis
 P -   Pneumonia
 Tr -  Tubercular
 Ts -  Tuberculosis
 U -   Ulceration

 ----------------------------------------------------------------------
          SHOWING THE FREQUENT COMPLICATION OF NODULAR LEPROSY
                           WITH TUBERCULOSIS.
 ---+----+---------------+----------+----------+----------+------------
    |    |  LUNGS AND    |          |          |          | INTESTINAL
 NO.| D. |   PLEURA.     |  LIVER.  | SPLEEN.  | KIDNEYS. |   CANAL.
 ---+----+---------------+----------+----------+----------+------------
  1 | 11 | Normal.       | A and L. | A and L. | F.       | Amyloid.
  2 |  6 |      [1]      | Leprous. | Tr.      | F.       | Normal.
  3 | 10 | Hydro-thorax. | A and L. | Leprous. |     ?    | Normal.
  4 |  5 |      [2]      | Leprous. | Amyloid. | Amyloid. | A and Tr U.
  5 | 12 | Normal.       | Amyloid. | Amyloid. | Amyloid. | Normal.
  6 |  8 | Lobular P in  | Leprous. | Leprous. | F.       | Normal.
    |    |  the right    |          |          |          |
    |    |  lung.        |          |          |          |
  7 | 13 | Lungs         | Leprous. | Leprous. | F.       | Normal.
    |    |  œdematous.   |          |          |          |
  8 |  7 |      [3]      | Leprous. | Leprous. | Normal.  | Normal.
  9 |  5 |      [4]      | A and L. | Leprous. | A and F. | Amyloid.
 10 |  6 | Œdema.        | Leprous. | Leprous. | F.       | Normal.
 11 |  5 |      [5]      | A and L. | A and L. | Amyloid. | Amyloid.
 12 | 11 | Normal.       | Leprous. | Leprous. | NpI.     | Normal.
 13 |  9 |      [6]      | A & L.   | L (?).   | A and    | A and Tr,
    |    |               |  (?)     |          |  Tr.     |  Tr peri-
    |    |               |          |          |          |  tonitis.
 14 | 10 | Normal.       | A and L. | Leprous. | Amyloid. | A U in the
    |    |               |          |          |          |  ileum.
 15 | 14 | Tr peri-      | Tr.      | Tr.      | A and    | A and Ts
    |    |  bronchitis   |          |          |  Tr.     |  of omentum
    |    |  and          |          |          |          |  and
    |    |  pleurisy.    |          |          |          |  mesentery.
 16 |  4 | Tr peri-      | Tr, A,   | Tr and A | Tr and   | A, Tr U,
    |    |  bronchitis   |  and L.  |  and L.  |  A.      |  mesenteric
    |    |  and          |          |          |          |  Ts.
    |    |  pleurisy.    |          |          |          |
 17 |  7 | Normal.       | L and A. | L and A. | Amyloid. | Amyloid.
 18 | 10 | Numerous      | L and A. | L and A. | F.       |    [7]
    |    |  cavities and |          |          |          |
    |    |  gelatinous   |          |          |          |
    |    |  pneumonia.   |          |          |          |
 19 |  6 | Numerous      | Leprous. | Leprous. | NpI.     | Ulcerating
    |    |  cavities and |          |          |          |  plaques
    |    |  gelatinous   |          |          |          |  and
    |    |  pneumonia.   |          |          |          |  solitary
    |    |               |          |          |          |  glands.
 20 | 15 | Normal.       | F.       | Amyloid. | Amyloid. | Amyloid.
 21 |  2 | Normal.       | Leprous. | Leprous. | Normal.  | Normal.
 22 | 14 | A small P     | Leprous. | Leprous. | A and F. | Amyloid.
    |    |  in R.        |          |          |          |
 23 |  7 |     [8]       | Leprous. | L and A. | A and F. | Tr U.
 24 | 13 | Bronchi-      | Leprous. | Leprous. | A and F. | Normal.
    |    |  ectasis and  |          |          |          |
    |    |  lobular P.   |          |          |          |
 25 |  8 | Bronchi-      | Leprous. | Leprous. | Slight   | Normal.
    |    |  ectasis and  |          |          |  F.      |
    |    |  lobular P.   |          |          |          |
 26 |  5 | Normal.       | Leprous. | Leprous. | Slight   | Normal.
    |    |               |          |          |  F.      |
 27 |  ? | Small cavi-   | L and A. | L and A. | Amyloid. | Normal.
    |    |  ties and     |          |          |          |
    |    |  lobular P.   |          |          |          |
 28 |  3 | Small cavi-   | L and    | L and    | F and A. | A ulcerated
    |    |  ties and     |  Tr.     |  Tr.     |          |  follicles
    |    |  lobular P.   |          |          |          |  and
    |    |               |          |          |          |  plaques.
 29 | 1½ | Ts of lungs   | L and    | L and    | NpA, Ts  | Normal.
    |    |  and pleura.  |  Tr.     |   Tr.    |  in R.   |
    |    |               |          |          |  kidney. |
 30 |  4 | Caseous areas | Leprous. | Leprous. |   [9]    | Normal.
    |    |  in both      |          |          |          |
    |    |  lungs.       |          |          |          |
 31 |  6 | Œdema,        | Amyloid. | Amyloid. | Amyloid. | Amyloid.
    |    |  bronchitis.  |          |          |          |
 32 | 24 | Lobular P.    | Amyloid. | Amyloid. | A and F. | Amyloid.
 33 |  6 | Cavities and  | L and A. | L and A. | Normal.  | Amyloid.
    |    |   lobular P.  |          |          |          |
 34 |  5 | Normal.       | Leprous. | L and A. | A & NpI. | Amyloid.
 35 |  4 | Pleuritic     | Leprous. | Leprous. | Normal.  | Peritonitis,
    |    |  adhesions.   |          |          |          |  U of the
    |    |               |          |          |          |  vermiform
    |    |               |          |          |          |  process.
 36 | 14 | Œdema.        | Amyloid. | Normal.  | A and F. | Amyloid.
 37 |  4 | Left Tr pleu- | Amyloid. | A and    | Tr.      | A, Tr peri-
    |    |  risy; R. Tr  |          |  Tr.     |          |  tonitis.
    |    |  peri-        |          |          |          |
    |    |  bronchitis.  |          |          |          |
 38 |  6 |    [10]       | Leprous. | Leprous. | Normal.  |   [11]
 39 |  6 |    [12]       | L and A. | L and A. | Tr & A.  | Amyloid.
 40 |  7 | Normal.       | L and A. | L and A. | Amyloid. | Normal.
 41 |  8 | Lobular P.    | Leprous. | L and A. | Amyloid. | Normal.
 42 |  2 | Tubercular.   | L & Tr.  | L & Tr.  | Normal.  | Tr U.
 43 | 12 | Lobular P.    | Leprous. | Leprous. | A and F. | Normal.
 44 |  8 | Lobular P,    | L and A. | L and A. | NpA.     | Normal.
    |    |  pleurisy.    |          |          |          |
 45 | 4? | Cavities and  | L and A. | L and A. | Normal.  | Amyloid
    |    |  lobular      |          |          |          |  ulcer-
    |    |  caseous P.   |          |          |          |  ations.
 46 |  4 | Ts, double P. | Leprous. | Leprous. | Normal.  | Normal.
 47 | 10 | Œdema.        | Amyloid. | Amyloid. | Amyloid. | Amyloid.
 48 |  4 | Tuberculosis. | Tr and   | Amyloid. | Tr and   | A, Tr
    |    |               |  A.      |          |  A.      |  ulcer-
    |    |               |          |          |          |  ations.
 49 |  ? | Normal.       | L and A. | L and A. | Amyloid. | Amyloid.
 50 |  4 |    [13]       | Leprous. | Leprous. | Normal.  | Tr U.
 51 |  7 | Bronchi-      | Leprous. | Leprous. | Normal.  | Normal.
    |    |  ectasis,     |          |          |          |
    |    |  lobular P.   |          |          |          |
 52 |  ? | R. lobular P. | Leprous. | Leprous. | Normal.  | Normal.
 53 |  ? | Pleuritic     | Amyloid. | Amyloid. | Amyloid. | Amyloid.
    |    |  adhesions,   |          |          |          |
    |    |  lungs N.     |          |          |          |
 54 |  5 | Ts of lungs   | L, Tr,   | L and    | Amyloid. | A, Tr U.
    |    |  and pleura.  |  and A.  |  Tr.     |          |
 55 | 12 |    [14]       | L. (?)   |  [15]    | Nephr-   | Amyloid.
    |    |               |          |          |  itis.   |
 56 |  3 | Tuberculosis. | Cirrh-   | L (?)    | Normal.  | Normal.
    |    |               |  osis.   |          |          |
 57 | 13 | Normal.       | Normal.  | Normal.  | Amyloid. | Normal.
 58 |  7 | Apical Ts.    | Leprous. | Leprous. | NpI.     | Normal.
 59 | 21 | Œdema.        | L (?).   | L (?).   | NpP.     | Normal.
 60 |  2 | Ts, cavities. | Amyloid. | Amyloid. | A and    | Tubercular.
    |    |               |          |          |  Ts.     |
 61 | 10 | Normal.       | Fatty.   | Normal.  | NpP.     | Tr (?)
 62 |  9 | Croupous P.   | Amyloid. | Amyloid. | Amyloid. | Normal.
 63 |  7 | Œdema.        | Leprous. | Leprous. | Normal.  | Hyperæmia.
 64 |  7 | Lobular P.    | Normal.  | Leprous. | Normal.  | Normal.
 65 |  9 | Normal.       | Leprous. | Leprous. | NpP.     | Normal.
 66 |  3 | Tuberculosis. | Leprous. | Leprous. |   [16]   | Normal.
 67 |  ? |    [17]       | Fatty.   | Tr.      | ?        | Normal.
 68 |  ? |    [18]       | Leprous. | Leprous. | Normal.  | Normal.
 69 |  ? | Tuberculosis. | Normal.  | Normal.  | NpI.     | Normal.
 70 |  ? | Normal.       | L and A. | L and A. | NpP.     | Normal.
 71 |  ? | Normal.       | Leprous. | Leprous. | NpI.     | Normal.
 72 | 17 | Normal.       | Cancer-  | Leprous. | Normal.  | Normal.
    |    |               |  ous.    |          |          |
 73 |  7 | Tuberculosis. | L and A. | L and A. | Amyloid. | Normal.
 74 |  ? | Ts of lungs   | Tr.      | Tr.      | Tr.      | Tubercular.
    |    |  and pleura.  |          |          |          |
 75 |  ? | Œdema.        | Amyloid. | Amyloid. | Amyloid. | Amyloid.
 76 | 2- | Tuberculosis. | Tr & A.  | L and A. | Amyloid. | Tr., Tr.
    |  3 |               |          |          |          |  peri-
    |    |               |          |          |          |  tonitis.
 77 |  ? | Tuberculosis. | Leprous. | L & Tr.  | Normal.  | Tubercular.
 78 | 10 | Tuberculosis. | L and A. | Leprous. | Amyloid. | Amyloid.
 79 |  7 | Cavities.     | L and A. | Amyloid. | NpP.     | Normal.
 80 |  ? | Cavities.     | L & Tr.  | L & Tr.  | Normal.  | Tr.
 81 |  7 | Normal.       | L and A. | L and A. | Amyloid. | Amyloid.
 82 |  ? | Double P.     | Amyloid. | Amyloid. | NpP & A. | Amyloid.
 83 |  ? | Normal.       | Leprous. | Leprous. | Normal.  | Amyloid.
 84 |  ? | Œdema.        | L & can- | Leprous. | NpI.     | Normal.
    |    |               |  cerous. |          |          |
 85 |  ? | Œdema.        | L and A. | L and A. | NpI & A. | Normal.
 86 |  ? | Tuberculosis. | Leprous. | L & Tr.  | Normal.  | Tr.
 87 | 1½ | Tuberculosis. | L & Tr.  | L & Tr.  | Normal.  | Tr.
 88 |  ? | Normal.       | L and A. | Leprous. | NpP.     | ?
 89 |  ? | Tuberculosis. | L and A. | Leprous. | NpI & A. | Normal.


Footnotes
---------

  1 Left-sided Tr pleurisy; in lower lobes, lobular pneumonia.

  2 Cavities in both apices; Tr peri-bronchitis in the upper lobes.

  3 In both lower lobes pneumonia, with  commencing cavity formation.

  4 In the left lung, cavities in the apex, and widespread lobular
     pneumonia. The same without cavity formation in the R.

  5 In upper lobes, cavities, and lobular pneumonia.

  6 Cavities, tubercular peri-bronchitis, pleural tuberculosis.

  7 Peyer’s patches and solitary glands tubercular with commencing
     ulceration.

  8 Cavities, tubercular peri-bronchitis, and lobular pneumonia in
     left lung.

  9 R. tubercular, L. hydronephrosis, tubercular cystitis.

 10 Tubercular peri-bronchitis and lobular pneumonia; tubercular
     pleurisy in left lung.

 11 Amyloid, localised tubercular peritonitis around the spleen.

 12 Tubercular peri-bronchitis, lobular pneumonia and small cavities.

 13 Tuberculosis, numerous large cavities, tubercular pleurisy.

 14 Pleuro-pneumonia  on right side, hydro-thorax sinistra, hydro-
     pericardium, ascites.

 15 Leprous (?) commencing amyloid degeneration.

 16 Congested, otherwise normal.

 17 Double pleurisy, caseous node of the size of a walnut in the
     left lung.

 18 Marked stenosis of larynx. Both apices infiltrated.




_TABLE II._

THE PROPORTION OF TUBERCULOSIS IN MACULO-ANÆSTHETIC LEPROSY.

 ---+-----------+----------+----------+----------+--------+----------+---------
 NO.|BRAIN.     |SPINAL    |LUNGS.    |LIVER.    |SPLEEN. |KIDNEYS.  |NERVES.
    |           |CORD.     |          |          |        |          |
 ---+-----------+----------+----------+----------+--------+----------+---------
    |           |          |          |          |        |          |
  1 |Nothing.   |Nothing.  |Tuberc-   |Enlarge-  |Nothing.|Hyperæmia.|Ulnar
    |           |          |ular.     |ment and  |        |          |nerve
    |           |          |          |hyperæmia.|        |          |thickened
    |           |          |          |          |        |          |in the
    |           |          |          |          |        |          |under
    |           |          |          |          |        |          |third of
    |           |          |          |          |        |          |the upper
    |           |          |          |          |        |          |arm.
    |           |          |          |          |        |          |
  2 |Nothing.   |Nothing.  |Tuberc-   |Nothing.  |Nothing.|Enlarge-  |
    |           |          |ular.     |          |        |ment and  |
    |           |          |          |          |        |fatty     |
    |           |          |          |          |        |degener-  |
    |           |          |          |          |        |ation.    |
    |           |          |          |          |        |          |
  3 |Hydroceph. |Nothing.  |Tuberc-   |Fatty.    |Nothing.|Nothing.  |Ulnar
    |internus.  |          |ular.     |          |        |          |nerve
    |Thickening |          |          |          |        |          |thickened
    |of the pia |          |          |          |        |          |through-
    |mater.     |          |          |          |        |          |out a
    |Gelatinous |          |          |          |        |          |length
    |exudation  |          |          |          |        |          |of about
    |between    |          |          |          |        |          |10-15 cm.
    |pia and    |          |          |          |        |          |about the
    |arachnoid. |          |          |          |        |          |elbows.
    |           |          |          |          |        |          |Median
    |           |          |          |          |        |          |nerve
    |           |          |          |          |        |          |thickened
    |           |          |          |          |        |          |at the
    |           |          |          |          |        |          |wrist.
    |           |          |          |          |        |          |
  4 |Nothing.   |Not       |Tuberc-   |Fatty.    |Normal. |Fatty     |
    |           |examined. |ular.     |          |        |degener-  |
    |           |          |          |          |        |ation.    |
    |           |          |          |          |        |          |
  5 |Nothing.   |Not       |Normal.   |Fatty.    |Normal. |Fatty     |
    |           |examined. |          |          |        |degener-  |
    |           |          |          |          |        |ation.    |
    |           |          |          |          |        |          |
  6 |Nothing.   |Not       |Normal.   |Normal.   |Normal. |Granular, |
    |           |examined. |          |          |        |atrophic. |
    |           |          |          |          |        |Fatty     |
    |           |          |          |          |        |degener-  |
    |           |          |          |          |        |ation.    |
    |           |          |          |          |        |          |
  7 |Solitary   |          |          |          |        |Tubercu-  |
    |tubercle   |          |          |          |        |losis of  |
    |in the     |          |          |          |        |the left  |
    |cerebellum.|          |          |          |        |kidney.   |
    |Hydroceph. |          |          |          |        |          |
    |internus.  |          |          |          |        |          |
    |           |          |          |          |        |          |
  8 |           |Not       |Normal.   |Fatty.    |        |Fatty     |Ulnar
    |           |examined. |          |          |        |degener-  |nerve
    |           |          |          |          |        |ation.    |as thick
    |           |          |          |          |        |          |as a
    |           |          |          |          |        |          |little
    |           |          |          |          |        |          |finger.
    |           |          |          |          |        |          |
  9 |           |Not       |Tuberc-   |Tubercu-  |Amyloid.|Hyperæmia.|Ulnar
    |           |examined. |ular.     |losis of  |        |Fatty     |nerve
    |           |          |          |periton-  |        |degener-  |contrac-
    |           |          |          |eum. Liver|        |ation.    |ted.
    |           |          |          |amyloid.  |        |          |
    |           |          |          |          |        |          |
 10 |Hydroceph. |Not       |Tuberc-   |Tuberc-   |Normal. |Normal.   |
    |internus.  |examined. |ular.     |ular.     |        |          |
    |           |          |          |          |        |          |
 11 |Normal.    |Not       |          |Amyloid.  |Amyloid.|Amyloid.  |
    |           |examined. |          |          |        |          |
    |           |          |          |          |        |          |
 12 |Normal.    |Not       |Tuberc-   |Hyper-    |Abscess.|Abscess.  |
    |           |examined. |ular.     |trophic.  |        |          |
    |           |          |          |          |        |          |
 13 |Tubercular |Not       |Miliary   |Miliary   |Miliary |          |
    |meningitis.|examined. |tubercu-  |tubercu-  |tubercu-|          |
    |           |          |losis.    |losis.    |losis.  |          |
    |           |          |          |          |        |          |
 14 |           |Degener-  |          |Fatty and |Amyloid.|Fatty     |Ulnar
    |           |ation of  |          |amyloid.  |        |degener-  |nerve
    |           |the pos-  |          |          |        |ation and |scler-
    |           |terior    |          |          |        |amyloid.  |otic.
    |           |columns.  |          |          |        |          |
    |           |          |          |          |        |          |
 15 |           |          |          |Fatty and |Amyloid.|Fatty     |Ulnar
    |           |          |          |amyloid.  |        |degener-  |nerve
    |           |          |          |          |        |ation and |scler-
    |           |          |          |          |        |amyloid.  |otic.
    |           |          |          |          |        |          |
 16 |Hydroceph. |Normal.   |Normal.   |Hyper-    |        |          |
    |internus.  |          |          |trophy    |        |          |
    |           |          |          |(?).      |        |          |
    |           |          |          |          |        |          |
 17 |Normal.    |Lumbar    |Normal.   |Normal.   |Normal. |Normal.   |
    |           |cord      |          |          |        |          |
    |           |thickened,|          |          |        |          |
    |           |the mem-  |          |          |        |          |
    |           |branes    |          |          |        |          |
    |           |thickened |          |          |        |          |
    |           |and       |          |          |        |          |
    |           |hyperæmic.|          |          |        |          |
    |           |          |          |          |        |          |
 18 |Normal.    |Thin,     |Normal.   |Large.    |Normal. |Normal.   |Axillary
    |           |atrophic  |          |          |        |          |plexus
    |           |(?).      |          |          |        |          |atrophic.
    |           |          |          |          |        |          |Ulnar and
    |           |          |          |          |        |          |radial
    |           |          |          |          |        |          |nerves
    |           |          |          |          |        |          |thick-
    |           |          |          |          |        |          |ened.
    |           |          |          |          |        |          |
 19 |           |          |          |Amyloid.  |Amyloid.|Inter-    |
    |           |          |          |Intestine |        |stitial   |
    |           |          |          |also      |        |nephritis.|
    |           |          |          |amyloid.  |        |          |
    |           |          |          |          |        |          |
 20 |           |          |          |          |Amyloid.|Amyloid.  |
    |           |          |          |          |        |          |
 21 |           |          |          |          |        |Inter-    |Ulnar
    |           |          |          |          |        |stitial   |nerve
    |           |          |          |          |        |nephritis.|scler-
    |           |          |          |          |        |          |osed.
    |           |          |          |          |        |          |
 22 |           |          |Tuberc-   |Amyloid.  |        |          |
    |           |          | ular.    |          |        |          |
    |           |          |          |          |        |          |
 23 |Normal.    |Normal.   |          |          |        |          |
    |           |          |          |          |        |          |
 24 |Normal.    |Normal.   |Double    |          |        |          |
    |           |          |pleurisy. |          |        |          |
    |           |          |          |          |        |          |
 25 |Sero-      |Normal.   |          |Fatty     |        |          |
    |purulent   |          |          |degenera- |        |          |
    |meningitis.|          |          |tion      |        |          |
    |           |          |          |          |        |          |
    |           |          |          |          |        |          |
 26 |Normal.    |Normal.   |          |          |        |          |
    |           |          |          |          |        |          |
 27 |Normal.    |Normal.   |          |          |        |          |
    |           |          |          |          |        |          |
 28 |           |          |Tuberc-   |Fatty     |Tuberc- |          |
    |           |          |ular.     |degenera- |ular.   |          |
    |           |          |          |tion.     |        |          |
    |           |          |          |(Intes-   |        |          |
    |           |          |          |tine also |        |          |
    |           |          |          |tuberc-   |        |          |
    |           |          |          |ular.)    |        |          |
    |           |          |          |          |        |          |
 29 |Normal.    |Normal.   |          |Amyloid.  |Amyloid.|Fatty     |
    |           |          |          |          |        |degener-  |
    |           |          |          |          |        |ation.    |
    |           |          |          |          |        |          |
 30 |Normal.    |Normal.   |          |Amyloid.  |Amyloid.|Amyloid.  |Ulnar
    |           |          |          |          |        |          |nerve
    |           |          |          |          |        |          |contr-
    |           |          |          |          |        |          |acted.
    |           |          |          |          |        |          |
 31 |           |          |Tuberc-   |Normal.   |Normal. |          |
    |           |          |ular.     |(Intes-   |        |          |
    |           |          |          |tine also |        |          |
    |           |          |          |tuberc-   |        |          |
    |           |          |          |ular.)    |        |          |
    |           |          |          |          |        |          |
 32 |           |          |Tuberc-   |Amyloid.  |Amyloid.|Nephritis |
    |           |          |ular.     |          |        |parenchym-|
    |           |          |          |          |        |atous.    |
    |           |          |          |          |        |          |
 33 |           |          |          |Fatty.    |Normal. |Tubercu-  |
    |           |          |          |(Intes-   |        |losis of  |
    |           |          |          |tine also |        |the left  |
    |           |          |          |tuberc-   |        |kidney.   |
    |           |          |          |ular.)    |        |          |
    |           |          |          |          |        |          |
 34 |           |          |Croupous  |          |        |Cirrhotic |
    |           |          |pneumonia.|          |        |kidney.   |
    |           |          |          |          |        |          |
 35 |           |          |Tuberc-   |Tuberc-   |Tuberc- |Fatty     |
    |           |          |ular.     |ulous.    |ulous.  |degener-  |
    |           |          |          |          |        |ation.    |
    |           |          |          |          |        |Amyloid.  |
    |           |          |          |          |        |          |
 36 |           |Degener-  |          |          |        |          |
    |           |ation of  |          |          |        |          |
    |           |the       |          |          |        |          |
    |           |posterior |          |          |        |          |
    |           |columns.  |          |          |        |          |
    |           |Atrophy   |          |          |        |          |
    |           |of the    |          |          |        |          |
    |           |posterior |          |          |        |          |
    |           |roots     |          |          |        |          |
    |           |Sclerosis |          |          |        |          |
    |           |of the    |          |          |        |          |
    |           |spinal    |          |          |        |          |
    |           |ganglia.  |          |          |        |          |
    |           |          |          |          |        |          |




_TABLE III._--THE PROPORTIONS OF THE TWO FORMS OF LEPROSY.

 +------------------+-------------------------------------------------+
 |                  | OF EVERY HUNDRED LEPERS FROM 1856 TO 1890 THERE |
 |                  |                 BELONGED TO THE                 |
 |                  |      NODULAR FORM:     |MACULO-ANÆSTHETIC FORM: |
 +                  +--------+------+--------+--------+------+--------+
 |                  |Altoget-|Males.|Females.|Altoget-|Males.|Females.|
 |                  |  her.  |      |        |  her.  |      |        |
 +------------------+--------+------+--------+--------+------+--------+
 | In the Eastern   |        |      |        |        |      |        |
 |   part of Norway |  47.7  | 26.6 |  21.1  |  52.3  | 27.5 |  24.8  |
 | Littoral         |        |      |        |        |      |        |
 |   Districts.     |        |      |        |        |      |        |
 |   { Lister       |        |      |        |        |      |        |
 |   {   and Mandal |  58.8  | 41.2 |  17.6  |  41.1  | 29.4 |  11.7  |
 |   { Stavanger    |  60.6  | 34.7 |  25.9  |  39.3  | 21.0 |  18.3  |
 |   { Söndre       |        |      |        |        |      |        |
 |   {   Bergenhus  |  68.0  | 34.2 |  33.8  |  31.9  | 15.3 |  16.6  |
 |   { Nordre       |        |      |        |        |      |        |
 |   {   Bergenhus  |  66.8  | 34.9 |  31.9  |  33.0  | 17.2 |  15.8  |
 |   { Romsdal      |  73.3  | 44.4 |  28.9  |  27.2  | 15.8 |  11.4  |
 |   { Söndre       |        |      |        |        |      |        |
 |   {   Trondhjem  |  74.3  | 48.5 |  25.8  |  25.7  | 16.4 |   9.3  |
 |   { Nordre       |        |      |        |        |      |        |
 |   {   Trondhjem  |  70.6  | 46.8 |  23.8  |  29.5  | 17.4 |  12.1  |
 |   { Nordland     |  71.5  | 44.1 |  27.4  |  28.5  | 17.1 |  11.4  |
 |   { Tromsö       |  79.1  | 52.9 |  26.2  |  20.9  | 13.1 |   7.8  |
 |   { Finmarken    |  82.5  | 65.0 |  17.5  |  17.5  | 12.5 |   5.0  |
 | Sogn             |  56.6  | 31.8 |  24.8  |  43.4  | 23.0 |  20.4  |
 | Söndfjord        |  72.6  | 37.4 |  35.2  |  27.4  | 14.3 |  13.1  |
 | Nordfjord        |  68.5  | 33.9 |  34.6  |  31.3  | 16.9 |  14.4  |
 + -----------------+--------+------+--------+--------+------+--------+




_TABLE IV._

 ------------------------------------------------------------------------
                    THE RESULTS OF ISOLATION IN NORWAY
 -----+----------+-------+-----------------------+----------------+------
      |          |       |                       | Number at end  |
      | Total at |       |       Result.         |    of Year.    | Total
      | commence-|       +------+-------+--------+----------------+at end
      |   ment   |  New  |      |       |  Emi-  |  At  |   In    |   of
 Year.| of Year. | Cases.| Died.| Cured.| grated.| Home.| Asylums.| Year.
 -----+----------+-------+------+-------+--------+------+---------+------
 1856 |   --     |  238  |  ?   |   ?   |   ?    | 2598 |   235   |  2833
 1857 |  2833    |  242  |  293 |   3   |  15    | 2339 |   427   |  2766
 1858 |  2766    |  210  |  224 |   3   |   3    | 2294 |   475   |  2769
 1859 |  2769    |  239  |  213 |   8   |   7    | 2267 |   523   |  2790
 1860 |  2790    |  219  |  251 |   1   |   6    | 2218 |   539   |  2757
 1861 |  2757    |  219  |  239 |   6   |  14    | 2028 |   711   |  2739
 1862 |  2739    |  211  |  215 |   5   |  11    | 2009 |   698   |  2707
 1863 |  2707    |  196  |  192 |   5   |   4    | 1947 |   749   |  2696
 1864 |  2696    |  201  |  202 |  --   |   8    | 1914 |   781   |  2695
 1865 |  2695    |  201  |  205 |   5   |   8    | 1910 |   772   |  2682
 1866 |  5682    |  203  |  214 |   3   |  10    | 1879 |   795   |  2674
 1867 |  2674    |  200  |  191 |   8   |   4    | 1876 |   787   |  2663
 1868 |  2663    |  206  |  210 |   6   |   7    | 1865 |   788   |  2653
 1869 |  2653    |  183  |  199 |  10   |  13    | 1820 |   787   |  2607
 1870 |  2607    |  187  |  203 |   4   |  13    | 1762 |   764   |  2526
 1871 |  2526    |  170  |  238 |   2   |  16    | 1681 |   747   |  2428
 1872 |  2428    |  131  |  205 |   5   |  10    | 1627 |   708   |  2335
 1873 |  2335    |  129  |  177 |   9   |  17    | 1592 |   672   |  2264
 1874 |  2264    |  137  |  183 |   6   |   9    | 1566 |   643   |  2209
 1875 |  2209    |  134  |  203 |   5   |  14    | 1499 |   623   |  2122
 1876 |  2122    |  115  |  187 |   3   |   6    | 1440 |   613   |  2053
 1877 |  2053    |  110  |  163 |   3   |   7    | 1372 |   629   |  2001
 1878 |  2001    |  105  |  149 |  10   |   8    | 1341 |   618   |  1959
 1879 |  1959    |   88  |  162 |   5   |  10    | 1277 |   602   |  1879
 1880 |  1879    |   72  |  150 |   7   |   7    | 1178 |   617   |  1795
 1881 |  1795    |   60  |  164 |   5   |   8    | 1092 |   608   |  1692
 1882 |  1692    |   66  |  137 |  11   |   7    | 1061 |   553   |  1614
 1883 |  1614    |   87  |  127 |   9   |   5    | 1022 |   535   |  1557
 1884 |  1557    |   55  |  140 |  10   |   2    |  944 |   519   |  1463
 1885 |  1463    |   71  |  146 |   9   |  12    |  855 |   522   |  1377
 1886 |  1377    |   48  |  135 |  16   |   9    |  748 |   522   |  1270
 1887 |  1270    |   47  |  111 |   2   |   3    |  704 |   514   |  1218
 1888 |  1218    |   27  |   99 |   8   |   1    |  631 |   524   |  1156
 1889 |  1156    |   27  |   86 |   9   |  12    |  551 |   530   |  1081
 1890 |  1081    |   10  |  122 |   6   |   2    |  447 |   507   |   954




PLATE VI.


_PLATE VI._

  _Fig. 1._--Two cells from a fresh nodule in 1 per cent. osmic acid
  (Gundlach, No. viii).

  _Fig. 2._--Part of a section of a cutaneous leproma. Round cells with
  clear stellate cells between them (Hartnack, No. ix).

  _Fig. 3._--From a corneal leproma. Round cells with corneal
  corpuscles between them (Hartnack, No. ix).

  _Fig. 4._--From the border of a corneal leproma. Capillary surrounded
  by round cells. Müller’s Fluid (Hartnack, No. ix).

  _Fig. 5._--From the inside of a corneal leproma. A capillary
  surrounded by round cells in among globi and corneal corpuscles
  unchanged or filled with brown granules. Müller’s Fluid (Hartnack,
  No. ix).

  _Fig. 6._--The brushed-out network of a cutaneous leproma (Hartnack,
  No. ix).

  _Fig. 7._--From a corneal leproma. Capillary surrounded by round
  cells free from bacilli, and outside these, cells filled with
  bacilli. Seibert homogen. immersion 1/16.

  _Fig. 8._--Cells from a cutaneous leproma. Eosin, Bismarck brown, and
  Gentian-violet. Hardening in Fleming’s Solution. Seibert homogen.
  immersion 1/16.

[Illustration: PLATE VI.]




PLATE VII.


_PLATE VII._

  _Fig. 1._--Cells and globi from cutaneous lepromata. Müller’s Fluid
  (Hartnack, No. ix).

  _Fig. 2._--Globi from a leprous spleen.

  _Fig. 3._--Two globi from the retina.

[Illustration: PLATE VII.]




PLATE VIII.


_PLATE VIII._

  _Fig. 1._--Corneal corpuscles filled with brown granules (Hartnack,
  No. ix).

  _Fig. 2._--From a leproma of the iris. Round cells with stellate
  cells (Hartnack, No. ix).

  _Fig. 3._--Corneal space with round cells near the corneal corpuscles
  (Hartnack, No. ix).

  _Fig. 4._--Cells with two nuclei full of bacilli from a cutaneous
  leproma. Seibert homog. immersion 1/16.

  _Fig. 5._--Two cells with bacilli from a leprous spleen. Fuchsin,
  methyl blue. Seibert homog. immersion 1/16.

  _Fig. 6._--From a leprous liver. White blood corpuscles with bacilli
  in a capillary. Seibert homog. immersion 1/16.

[Illustration: PLATE VIII.]




PLATE IX.


_PLATE IX._

  _Fig. 1._--From a leprous liver. Bacilli in an endothelial cell of a
  capillary. Seibert homog. immersion 1/16.

  _Fig. 2._--Piece of a very leprous liver. Capsule below, cut surface
  above.

  _Fig. 3._--Cut surface of a very leprous spleen.

  _Figs._ 4 and _5_ and _Plate X_, _Fig. 1._--Cross section of the
  seminal canals with bacilli around the nuclei of the walls and in
  the epithelium; in _Plate X_, _Fig. 1_, is shown an epithelial cell
  filled with bacilli.

[Illustration: PLATE IX.]




PLATE X.


_PLATE X._

  _Fig. 1._--Epithelial cell from a seminal canal, filled with bacilli.

  _Fig. 2._--A globus with a vacuole in which are fragments stained
  with Bismarck brown, probably the remains of nuclei.

  _Fig. 3._--A globus lying in a cell; the nucleus and a part of the
  cell-protoplasm preserved.

  _Fig. 4._--An epithelial cell from a seminal canal, filled with
  bacilli broken down into granules.

  _Fig. 5._--Cross section of a blood-vessel with bacilli in the
  endothelium and a white blood corpuscle filled with bacilli.

  _Fig. 6._--Longitudinal section of a blood-vessel showing bacilli in
  the endothelium, and a fibrinous coagulum enclosing two white blood
  corpuscles, one of them filled with bacilli.

  _Fig. 7._--Bacilli free between the red blood corpuscles.

  _Fig. 8._--A connective tissue space from the tunica albuginea filled
  with bacilli.

  _Fig. 9._--Cross section of a blood-vessel with bacilli around the
  nuclei of the surrounding connective tissue.

  All the preparations from the testicle were hardened in Fleming’s
  or Müller’s solutions, and the drawings made with a Seibert homog.
  immersion lens 1/16. _Plate IX_, _Fig. 5_ with Seibert 1/8.

[Illustration: PLATE X.]




PLATE XI.


_PLATE XI._

  _Fig. 1._--Bundle of nerve fibres from a ciliary nerve, the cells of
  Schwann’s sheath filled with brown granules.

  _Fig. 2._--The myelin sheath pressed in by a cell filled with
  granules.

  _Fig. 3._--Section from an old leprous macule.

  _Fig. 4._--Section from a recent leprous macule.

  Both sections stained with Fuchsin and Methyl-green. Seibert homogen.
  immersion 1/16.

[Illustration: PLATE XI.]




PLATE XII.


_PLATE XII._

  _Fig. 1._--Cross section of a leprous ulnar nerve. The darkly hatched
  cells represent those filled with brown granules. It will be noted
  that the axial cylinder is wanting in many of the nerve fibres
  (Hartnack, No. ix).

  _Fig. 2._--A piece of neurilemma with flat connective tissue cells
  lying on it, containing brown granules darkened by osmic acid
  (Gundlach, No. viii).

[Illustration: PLATE XII.]




PLATE XIII.


_PLATE XIII._

  _Fig. 1._--Cross section of an atrophic muscle, growth of nuclei in
  the perimysium. Low power.

  _Fig. 2._--Cross section of an atrophic muscle with great development
  of connective tissue. Low power.

  _Fig. 3._--Proliferation of the nuclei of the perimysium. High power.

[Illustration: PLATE XIII.]




TRANSCRIBER’S NOTE-

1. Enclosed italics font in _underscores_.

2. Hyphenation has been standardized.

2. _TABLE I._: Abbreviations have been used as shown in the Key. Longer
entries have been replaced by indexes to Footnotes, which are listed at
the foot of the Table.